Thursday, May 9, 2019

Genentech to Present New Data Highlighting Comprehensive Approach to Cancer Care at 2019 American Society Of Clinical Oncology (ASCO) Annual Meeting

Study results across 17 medicines reflect our commitment to personalized care with advances in targeted therapies, immunotherapy, and diagnostics, data and analytics

New pivotal data on fixed-duration combination of Venclexta plus Gazyva in previously untreated chronic lymphocytic leukemia

New data for entrectinib in pediatric patients with recurrent or refractory solid tumors harboring NTRK, ROS1 or ALK gene fusions

South San Francisco, CA -- May 9, 2019 --

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that new data from clinical trials of 17 approved and investigational medicines across 27 cancer types, including hard-to-treat and rare tumors, will be presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago from May 31-June 4, 2019. A total of 155 abstracts that include a Genentech medicine will be presented at this year's meeting.

"At this year’s ASCO meeting, we are excited to present new data with targeted therapies, immunotherapy and pipeline combinations across a broad range of diseases including blood, breast and lung cancers, as well as pediatric tumors treated with our personalized cancer medicine, entrectinib,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “Through pioneering science, strategic partnerships and data and analytics, we’re striving to develop transformative medicines that can help improve outcomes for each individual patient.”

For more resources, information and unique perspectives from scientists, researchers and physicians on key industry topics, visit http://www.gene.com/asco. Keep up to date on ASCO meeting news and updates by following Genentech on Twitter via @genentech and using the hashtag #ASCO19.

Key presentations in blood cancers

The first data from the pivotal Phase III CLL14 study will be presented at ASCO, evaluating the 12-month, fixed-duration, chemotherapy-free combination of Venclexta^® (venetoclax) plus Gazyva^® (obinutuzumab) compared to Gazyva plus chlorambucil in people with previously untreated chronic lymphocytic leukemia (CLL) and co-existing medical conditions. The CLL14 study is being conducted in cooperation with the German CLL Study Group (GCLLSG), headed by Michael Hallek, M.D., University of Cologne.

The U.S. Food and Drug Administration (FDA) is reviewing a supplemental New Drug Application (sNDA) based on results of the CLL14 study under the FDA’s Real-Time Oncology Review and Assessment Aid pilot programs. Venclexta is being developed by AbbVie and Genentech, a member of the Roche Group.

Key presentations in pediatric cancers

The first data from the Phase I/II STARTRK-NG study of the investigational medicine entrectinib in children and adolescents with recurrent or refractory solid tumors harboring neurotrophic tyrosine receptor kinase (NTRK), ROS1 or anaplastic lymphoma kinase (ALK)-positive tumors, including central nervous system tumors, will be presented. The study enrolled children and adolescents ages 4.9 months through 20 years (median age of seven years) across several different cancer types, including some rare tumors. The STARTRK-NG data will be featured as part of ASCO’s official press program on Wednesday, May 15.

The FDA recently granted Priority Review for entrectinib for the treatment of pediatric and adult patients with NTRK fusion-positive, locally advanced or metastatic solid tumors who have either progressed following prior therapies or as initial therapy when there are no acceptable standard therapies, and for the treatment of people with metastatic, ROS1-positive non-small cell lung cancer (NSCLC). These NDAs are based on results from the integrated analysis of the pivotal Phase II STARTRK-2, Phase I STARTRK-1 and Phase I ALKA-372-001 trials, and data from the STARTRK-NG study. The FDA is expected to make a decision on the approval by August 18, 2019.

Key presentations in breast cancers

Key data to be presented at ASCO include updates from Genentech’s breast cancer program across multiple subtypes of the disease, including the second interim analysis of overall survival (OS) results, updated safety data and patient-reported outcomes (PROs) from the Phase III IMpassion130 study of Tecentriq^® (atezolizumab) plus chemotherapy (Abraxane ^® [paclitaxel protein-bound particles for injectable suspension (albumin-bound); nab-paclitaxel]) for the treatment of PD-L1-positive, metastatic triple-negative breast cancer (TNBC). This combination was recently granted accelerated approval from the FDA based on progression-free survival (PFS) for the treatment of adults with unresectable locally advanced or metastatic TNBC in people whose tumors express PD-L1, as determined by an FDA-approved test.

Additional data include an eight-year, end-of-study analysis from the Phase III CLEOPATRA study of Perjeta^® (pertuzumab) plus Herceptin^® (trastuzumab) and chemotherapy for first-line treatment of HER2-positive metastatic breast cancer.

Key presentations in lung cancers

Key data from Genentech’s broad lung cancer program will be presented across different types of the disease, including results from the Phase III IMpower150 trial of Tecentriq plus Avastin^® (bevacizumab) and chemotherapy (carboplatin and paclitaxel) in chemotherapy-naïve people previously untreated for metastatic NSCLC whose cancer has spread to the liver, which affects approximately 20% of people with the disease. Additionally, results from studies in partnership with Flatiron Health will be presented, including validation of the use of next-generation sequencing data on a broad scale to improve the understanding of clinical outcomes in people with metastatic lung cancer, and results that illustrate how real-world data can be used to supplement evidence from clinical trials in rare tumor types such as ROS1-positive lung cancer.

Key presentations featuring Genentech medicines at ASCO 2019

Medicine	Abstract title	Abstract number
Blood cancer
Venclexta (venetoclax) Gazyva (obinutuzumab)	Effect of fixed-duration venetoclax plus obinutuzumab (VenG) on progression-free survival (PFS), and rates and duration of minimal residual disease negativity (MRD–) in previously untreated patients (pts) with chronic lymphocytic leukemia (CLL) and comorbidities	Abstract 7502 (oral) Tuesday, June 4 10:09 – 10:21 AM CDT
Venclexta	Safety and activity of venetoclax in combination with high-dose cytarabine in children with relapsed or refractory acute myeloid leukemia	Abstract 10004 (oral) Friday, May 31 3:57 – 4:09 PM CDT
polatuzumab vedotin	Polatuzumab vedotin (Pola) + obinutuzumab (G) and lenalidomide (Len) in patients (pts) with relapsed/refractory (R/R) follicular lymphoma (FL): Interim analysis of a Phase Ib/II trial	Abstract 7505 (oral) Tuesday, June 4 11:33 – 11:45 AM CDT
Tumor agnostic
entrectinib	Phase I/II trial to assess the activity of entrectinib in children and adolescents with recurrent or refractory solid tumors including central nervous system (CNS) tumors	Abstract 10009 (oral) Sunday, June 2 8:00 – 8:12 AM CDT
entrectinib	Efficacy of entrectinib in patients (pts) with solid tumors and central nervous system (CNS) metastases: Integrated analysis from three clinical trials	Abstract 3017 (poster) Saturday, June 1 8:00 – 11:00 AM CDT
Breast cancer
Tecentriq (atezolizumab)	IMpassion130: updated overall survival (OS) from a global, randomized, double-blind, placebo-controlled, Phase III study of atezolizumab (atezo) + nab-paclitaxel (nP) in previously untreated locally advanced or metastatic triple-negative breast cancer (mTNBC)	Abstract 1003 (oral) Tuesday, June 4 10:45 – 10:57 AM CDT
Perjeta (pertuzumab) Kadcyla (ado- trastuzumab emtansine) Herceptin (trastuzumab)	Neoadjuvant trastuzumab (H), pertuzumab (P), and chemotherapy versus trastuzumab emtansine (T-DM1) and P in human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC): Final outcome results from the Phase III KRISTINE study	Abstract 500 (oral) Monday, June 3 9:45 – 9:57 AM CDT
Perjeta Herceptin	Genomic correlates of response to adjuvant trastuzumab (H) and pertuzumab (P) in HER2+ breast cancer (BC): Biomarker analysis of the APHINITY trial	Abstract 1012 (clinical science symposium) Saturday, June 1 3:48 – 4:00 PM CDT
Perjeta Herceptin	End-of-study analysis from the phase III, randomized, double-blind, placebo (Pla)-controlled CLEOPATRA study of first-line (1L) pertuzumab (P), trastuzumab (H), and docetaxel (D) in patients (pts) with HER2-positive metastatic breast cancer (MBC)	Abstract 1020 (poster) Sunday, June 2 8:00 – 11:00 AM CDT
Tecentriq	IMpassion130: Expanded safety analysis from a P3 study of atezolizumab (A) + nab-paclitaxel (nP) in patients (pts) with treatment (tx)-naïve, locally advanced or metastatic triple-negative breast cancer (mTNBC)	Abstract 1068 (poster) Sunday, June 2 8:00 – 11:00 AM CDT
Tecentriq	Patient-reported outcomes (PROs) from the Phase III IMpassion130 trial of atezolizumab (atezo) plus nabpaclitaxel (nP) in metastatic triple-negative breast cancer (mTNBC)	Abstract 1067 (poster) Sunday, June 2 8:00 – 11:00 AM CDT
Kadcyla Herceptin	Patient-reported outcomes (PROs) from KATHERINE: A Phase III study of adjuvant trastuzumab emtansine (T-DM1) versus trastuzumab (H) in patients (pts) with residual invasive disease after neoadjuvant therapy for HER2-positive breast cancer	Abstract 513 (poster) Sunday, June 2 8:00 – 11:00 AM CDT
Perjeta Herceptin	A phase III, randomized, double-blind, placebo (Pla)-controlled study of pertuzumab (P) + trastuzumab (H) + docetaxel (D) versus Pla + H+ D in previously untreated HER2-positive locally recurrent/metastatic breast cancer (LR/MBC) (PUFFIN).	Abstract 1026 (poster) Sunday, June 2 8:00 – 11:00 AM CDT
Lung cancer
Tecentriq	IMpower150: Analysis of efficacy in patients (pts) with liver metastases (mets)	Abstract 9012 (poster discussion) Sunday, June 2 4:30 – 6:00 PM CDT
Tecentriq	Neoadjuvant atezolizumab in resectable non-small cell lung cancer (NSCLC): Interim analysis and biomarker data from a multicenter study (LCMC3)	Abstract 8503 (oral) Saturday, June 1 2:15 – 2:27 PM CDT
entrectinib	Time-to-treatment discontinuation (TTD) and real-world progression-free survival (rwPFS) as endpoints for comparative efficacy analysis between entrectinib trial and crizotinib real-world ROS1 fusion-positive (ROS1+) NSCLC patients	Abstract 9070 (poster) Sunday, June 2 8:00 – 11:00 AM CDT
Alecensa (alectinib)	Final PFS analysis and safety data from the phase III J-ALEX study of Alectinib(ALC) vs. Crizotinib(CRZ) in ALK-inhibitor naïve ALK-positive Non-Small Cell Lung Cancer (ALK+NSCLC)	Abstract 8569 (poster) Sunday, June 2 8:00 – 11:00 AM CDT
Genitourinary cancers
Tecentriq	Clinical outcomes according to PD-L1 status and age in the prospective international SAUL study of atezolizumab (atezo) for locally advanced or metastatic urothelial carcinoma (UC) or non-UC of the urinary tract	Abstract 4519 (poster) Monday, June 3 1:15 – 4:15 PM CDT

About Venclexta

Venclexta is a first-in-class targeted medicine designed to selectively bind and inhibit the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers and other tumors, BCL-2 builds up and prevents cancer cells from dying or self-destructing, a process called apoptosis. Venclexta blocks the BCL-2 protein and works to restore the process of apoptosis. Venclexta is being developed by AbbVie and Genentech, a member of the Roche Group. It is jointly commercialized by the companies in the United States and commercialized by AbbVie outside of the United States. Together, the companies are committed to research with Venclexta, which is currently being studied in clinical trials across several types of blood and other cancers.

Venclexta Indications

Venclexta is a prescription medicine used:

• To treat adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), with or without 17p deletion, who have received at least 1 prior treatment.
• In combination with azacitidine, or decitabine, or low-dose cytarabine to treat adults with newly-diagnosed acute myeloid leukemia (AML) who:
  • ‒ Are 75 years of age or older, or
  • ‒ Have other medical conditions that prevent the use of standard chemotherapy.

It is not known if Venclexta is safe and effective in children.

Important Safety Information

Venclexta can cause serious side effects, including:

Tumor lysis syndrome (TLS). TLS is caused by the fast breakdown of cancer cells. TLS can cause kidney failure, the need for dialysis treatment, and may lead to death. The patient’s doctor will do tests to check their risk of getting TLS before they start taking Venclexta. The patient will receive other medicines before starting and during treatment with Venclexta to help reduce the risk of TLS. The patient may also need to receive intravenous (IV) fluids through their vein.

The patient’s doctor will do blood tests to check for TLS when the patient first starts treatment and during treatment with Venclexta. It is important for patients to keep appointments for blood tests. Patients should tell their doctor right away if they have any symptoms of TLS during treatment with Venclexta, including fever, chills, nausea, vomiting, confusion, shortness of breath, seizures, irregular heartbeat, dark or cloudy urine, unusual tiredness, or muscle or joint pain.

Patients should drink plenty of water during treatment with Venclexta to help reduce the risk of getting TLS.

Patients should drink 6 to 8 glasses (about 56 ounces total) of water each day, starting 2 days before the first dose, on the day of the first dose of Venclexta, and each time a dose is increased.

The patient’s doctor may delay, decrease the dose, or stop treatment with Venclexta if the patient has side effects.

Certain medicines must not be taken when the patient first starts taking Venclexta and while the dose is being slowly increased because of the risk of increased tumor lysis syndrome.

• Patients must tell their doctor about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Venclexta and other medicines may affect each other, causing serious side effects.
• Patients must not start new medicines during treatment with Venclexta without first talking with their doctor.

Before taking Venclexta, patients must tell their doctor about all of their medical conditions, including if they:

• Have kidney problems.
• Have problems with body salts or electrolytes, such as potassium, phosphorus, or calcium.
• Have a history of high uric acid levels in the blood or gout.
• Are scheduled to receive a vaccine. The patient should not receive a “live vaccine” before, during, or after treatment with Venclexta, until the patient’s doctor tells them it is okay. If the patient is not sure about the type of immunization or vaccine, the patient should ask their doctor. These vaccines may not be safe or may not work as well during treatment with Venclexta.
• Are pregnant or plan to become pregnant. Venclexta may harm an unborn baby. If the patient is able to become pregnant, the patient’s doctor should do a pregnancy test before the patient starts treatment with Venclexta, and the patient should use effective birth control during treatment and for at least 30 days after the last dose of Venclexta. If the patient becomes pregnant or thinks they are pregnant, the patient should tell their doctor right away.
• Are breastfeeding or plan to breastfeed. It is not known if Venclexta passes into the patient’s breast milk. Patients should not breastfeed during treatment with Venclexta.

What to avoid while taking Venclexta:

Patients should not drink grapefruit juice, eat grapefruit, Seville oranges (often used in marmalades), or starfruit while they are taking Venclexta. These products may increase the amount of Venclexta in the patient’s blood.

Venclexta can cause serious side effects, including:

• Low white blood cell counts (neutropenia). Low white blood cell counts are common with Venclexta, but can also be severe. The patient’s doctor will do blood tests to check their blood counts during treatment with Venclexta. Patients should tell their doctor right away if they have a fever or any signs of an infection during treatment with Venclexta.

The most common side effects of Venclexta when used in combination with rituximab in people with CLL include low white blood cell counts; diarrhea; upper respiratory tract infection; cough;tiredness; and nausea.

The most common side effects of Venclexta when used alone in people with CLL/SLL include low white blood cell counts; diarrhea; nausea; upper respiratory tract infection; low red blood cell counts;tiredness; low platelet counts; muscle and joint pain; swelling of arms, legs, hands, and feet; and cough.

The most common side effects of Venclexta in combination with azacitidine, or decitabine, or low-dose cytarabine in people with AML include low white blood cell counts; nausea; diarrhea; low platelet counts; constipation; fever with low white blood cell counts; low red blood cell counts; infection in blood; rash; dizziness; low blood pressure; fever; swelling of arms, legs, hands, and feet; vomiting; tiredness; shortness of breath; bleeding; infection in lung; stomach (abdominal) pain; pain in muscles or back; cough; and sore throat.

Venclexta may cause fertility problems in males. This may affect the ability to father a child. Patients should talk to their doctor if they have concerns about fertility.

These are not all the possible side effects of Venclexta. Patients should tell their doctor about any side effect that bothers them or that does not go away.

Report side effects to the FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch. Report side effects to Genentech at 1-888-835-2555.

Please visit http://www.Venclexta.com for the Venclexta full Prescribing Information, including Patient Information, for additional Important Safety Information.

About Gazyva

Gazyva is an engineered monoclonal antibody designed to attach to CD20, a protein found only on certain types of B-cells. It is thought to work by attacking targeted cells both directly and together with the body's immune system. Gazyva was discovered by Roche Glycart AG, a wholly owned, independent research unit of Roche. In the United States, Gazyva is part of a collaboration between Genentech and Biogen.

Combination studies investigating Gazyva with other approved or investigational medicines, including cancer immunotherapies and small molecule inhibitors, are underway across a range of blood cancers. 

Gazyva Indications

Gazyva (obinutuzumab) is a prescription medicine used:

• With the chemotherapy drug, chlorambucil, to treat chronic lymphocytic leukemia (CLL) in adults who have not had previous CLL treatment.
• With the chemotherapy drug, bendamustine, followed by Gazyva alone for follicular lymphoma (FL) in adults who did not respond to a rituximab-containing regimen, or whose FL returned after such treatment.
• With chemotherapy, followed by Gazyva alone in those who responded, to treat stage II bulky, III, or IV FL in adults who have not had previous FL treatment.

Important Safety Information

The most important safety information patients should know about Gazyva

Patients must tell their doctor right away about any side effect they experience. Gazyva can cause side effects that can become serious or life threatening, including:

• Hepatitis B Virus (HBV): Hepatitis B can cause liver failure and death. If the patient has a history of hepatitis B infection, Gazyva could cause it to return. Patients should not receive Gazyva if they have active hepatitis B liver disease. The patient’s doctor or healthcare team will need to screen them for hepatitis B before, and monitor the patient for hepatitis during and after, their treatment with Gazyva. Sometimes this will require treatment for hepatitis B. Symptoms of hepatitis include: worsening of fatigue and yellow discoloration of skin or eyes
• Progressive Multifocal Leukoencephalopathy (PML): PML is a rare and serious brain infection caused by a virus. PML can be fatal. The patient’s weakened immune system could put them at risk. The patient’s doctor will watch for symptoms. Symptoms of PML include: confusion, difficulty talking or walking, dizziness or loss of balance, and vision problems

Who should not receive Gazyva:

Patients should NOT receive Gazyva if they have had an allergic reaction (e.g., anaphylaxis or serum sickness) to Gazyva.Patients must tell their healthcare provider if they have had an allergic reaction to obinutuzumab or any other ingredients in Gazyva in the past

Additional possible serious side effects of Gazyva:

Patients must tell their doctor right away about any side effect they experience. Gazyva can cause side effects that may become severe or life threatening, including:

• Infusion Reactions: These side effects may occur during or within 24 hours of any Gazyva infusion. Some infusion reactions can be serious, including, but not limited to, severe allergic reactions (anaphylaxis), acute life-threatening breathing problems, or other life-threatening infusion reactions. If the patient has a reaction, the infusion is either slowed or stopped until their symptoms are resolved. Most patients are able to complete infusions and receive medication again. However, if the infusion reaction is life threatening, the infusion of Gazyva will be permanently stopped. The patient’s healthcare team will take steps to help lessen any side effects the patient may have to the infusion process. The patient may be given medicines to take before each Gazyva treatment. Symptoms of infusion reactions may include: fast heartbeat, tiredness, dizziness, headache, redness of the face, nausea, chills, fever, vomiting, diarrhea, rash, high blood pressure, low blood pressure, difficulty breathing, and chest discomfort
• Hypersensitivity Reactions Including Serum Sickness: Some patients receiving Gazyva may have severe or life-threatening allergic reactions. This reaction may be severe, may happen during or after an infusion, and may affect many areas of the body. If an allergic reaction occurs, the patient’s doctor will stop the infusion and permanently discontinue Gazyva
• Tumor Lysis Syndrome (TLS): Tumor lysis syndrome, including fatal cases, has been reported in patients receiving Gazyva. Gazyva works to break down cancer cells quickly. As cancer cells break apart, their contents are released into the blood. These contents may cause damage to organs and the heart, and may lead to kidney failure requiring the need for dialysis treatment. The patient’s doctor may prescribe medication to help prevent TLS. The patient’s doctor will also conduct regular blood tests to check for TLS. Symptoms of TLS may include nausea, vomiting, diarrhea, and tiredness
• Infections: While the patient is taking Gazyva, they may develop infections. Some of these infections may be fatal and severe, so the patient should be sure to talk to their doctor if they think they have an infection. Patients administered Gazyva in combination with chemotherapy, followed by Gazyva alone are at a high risk of infections during and after treatment. Patients with a history of recurring or chronic infections may be at an increased risk of infection. Patients with an active infection should not be treated with Gazyva. Patients taking Gazyva plus bendamustine may be at higher risk for fatal or severe infections compared to patients taking Gazyva plus CHOP or CVP
• Low White Blood Cell Count: When the patient has an abnormally low count of infection-fighting white blood cells, it is called neutropenia. While the patient is taking Gazyva, their doctor will do blood work to check their white blood cell count. Severe and life-threatening neutropenia can develop during or after treatment with Gazyva. Some cases of neutropenia can last for more than one month. If the patient’s white blood cell count is low, their doctor may prescribe medication to help prevent infections
• Low Platelet Count: Platelets help stop bleeding or blood loss. Gazyva may reduce the number of platelets the patient has in their blood; having low platelet count is called thrombocytopenia. This may affect the clotting process. While the patient is taking Gazyva, their doctor will do blood work to check their platelet count. Severe and life-threatening thrombocytopenia can develop during treatment with Gazyva. Fatal bleeding events have occurred in patients treated with Gazyva. If the patient’s platelet count gets too low, their treatment may be delayed or reduced

The most common side effects of Gazyva in CLL were infusion reactions, low white blood cell counts, low platelet counts, low red blood cell counts, fever, cough, nausea, and diarrhea

The safety of Gazyva was evaluated based on 392 patients with relapsed or refractory NHL, including FL (81 percent), small lymphocytic lymphoma (SLL) and marginal zone lymphoma (MZL) (a disease for which Gazyva is not indicated), who did not respond to or progressed within 6 months of treatment with rituximab product or a rituximab product-containing regimen. In patients with follicular lymphoma, the profile of side effects that were seen were consistent with the overall population who had NHL. The most common side effects of Gazyva were infusion reactions, low white blood cell counts, nausea, fatigue, cough, diarrhea, constipation, fever, low platelet counts, vomiting, upper respiratory tract infection, decreased appetite, joint or muscle pain, sinusitis, low red blood cell counts, general weakness and urinary tract infection

A randomized, open-label multicenter trial (GALLIUM) evaluated the safety of Gazyva as compared to rituximab product in 1,385 patients with previously untreated follicular lymphoma (86%) or marginal zone lymphoma (14%).The most common side effects of Gazyva were infusion reactions, low white blood cell count, upper respiratory tract infection, cough, constipation and diarrhea

Before receiving Gazyva, patients should talk to their doctor about:

• Immunizations: Before receiving Gazyva therapy, the patient should tell their healthcare provider if they have recently received or are scheduled to receive a vaccine. Patients who are treated with Gazyva should not receive live vaccines
• Pregnancy: The patient should tell their doctor if they are pregnant, think that they might be pregnant, plan to become pregnant, or are breastfeeding. Gazyva may harm their unborn baby. The patient should speak to their doctor about using Gazyva while they are pregnant. The patient should talk to their doctor or their child’s doctor about the safety and timing of live virus vaccinations to their infant if they received Gazyva during pregnancy. It is not known if Gazyva may pass into the patient’s breast milk. The patient should speak to their doctor about using Gazyva if they are breastfeeding

Patients should tell their doctor about any side effects.

These are not all of the possible side effects of Gazyva. For more information, patients should ask their doctor or pharmacist.

Gazyva is available by prescription only.

Report side effects to the FDA at (800) FDA-1088, or http://www.fda.gov/medwatch. Report side effects to Genentech at (888) 835-2555.

Please visit http://www.Gazyva.com for the Gazyva full Prescribing Information, including BOXED WARNINGS, for additional Important Safety Information.

About Tecentriq

Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1. Tecentriq is designed to bind to PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the re-activation of T cells. Tecentriq may also affect normal cells.

Abraxane is a registered trademark of Abraxis Bioscience, LLC, a wholly owned subsidiary of Celgene Corporation.

Tecentriq U.S. Indications

Tecentriq is a prescription medicine used to treat adults with:

A type of bladder and urinary tract cancer called urothelial carcinoma. Tecentriq may be used when your bladder cancer:

• has spread or cannot be removed by surgery, and if you have any one of the following conditions:
  • you are not able to take chemotherapy that contains a medicine called cisplatin, and your doctor has tested your cancer and found high levels of a specific protein on your cancer called programmed death-ligand 1 (PD-L1), or
  • you are not able to take chemotherapy that contains any platinum regardless of the levels of “PD-L1” status, or
  • you have tried chemotherapy that contains platinum, and it did not work or is no longer working

The approval of Tecentriq in these patients is based on a study that measured response rate and duration of response. There is an ongoing study to confirm clinical benefit.

A type of lung cancer called non-small cell lung cancer (NSCLC).

• Tecentriq may be used with bevacizumab and the chemotherapy medicines carboplatin and paclitaxel as your first treatment when your lung cancer:
  • has spread or grown, and
  • is a type of lung cancer called “non-squamous NSCLC”
  • your tumor does not have an abnormal “EGFR” or “ALK” gene
• Tecentriq may be used alone when your lung cancer:
  • has spread or grown, and
  • you have tried chemotherapy that contains platinum, and it did not work or is no longer working, and
  • If your tumor has an abnormal EGFR or ALK gene, you should have also tried an FDA-approved therapy for tumors with these abnormal genes, and it did not work or is no longer working.

A type of breast cancer called triple-negative breast cancer (TNBC).

Tecentriq may be used with the medicine paclitaxel protein-bound when your breast cancer:

• has spread or cannot be removed by surgery, and
• your cancer tests positive for “PD-L1”

The approval of Tecentriq in these patients is based on a study that measured progression-free survival. There is an ongoing study to confirm clinical benefit.

A type of lung cancer called small cell lung cancer (SCLC).

• Tecentriq may be used with the chemotherapy medicines carboplatin and etoposide as your first treatment when your lung cancer:
  • is a type of lung cancer called “extensive-stage small cell lung cancer,” which means that it has spread or grown.

It is not known if Tecentriq is safe and effective in children.

Important Safety Information

What is the most important information about Tecentriq?

Tecentriq can cause the immune system to attack normal organs and tissues and can affect the way they work. These problems can sometimes become serious or life threatening and can lead to death.

Patients should call or see their healthcare provider right away if they get any symptoms of the following problems or these symptoms get worse.

Tecentriq can cause serious side effects, including:

• Lung problems (pneumonitis)–signs and symptoms of pneumonitis may include new or worsening cough, shortness of breath, and chest pain
• Liver problems (hepatitis)–signs and symptoms of hepatitis may include yellowing of your skin or the whites of your eyes, severe nausea or vomiting, pain on the right side of the stomach area (abdomen), drowsiness, dark urine (tea colored), bleeding or bruising more easily than normal, and feeling less hungry than usual
• Intestinal problems (colitis)–signs and symptoms of colitis may include diarrhea (loose stools) or more bowel movements than usual, blood or mucus in your stools or dark, tarry, sticky stools, and severe stomach area (abdomen) pain or tenderness
• Hormone gland problems (especially the thyroid, adrenal glands, pancreas, and pituitary) –signs and symptoms that the hormone glands are not working properly may include headaches that will not go away or unusual headaches, extreme tiredness, weight gain or weight loss, dizziness or fainting, feeling more hungry or thirsty than usual, hair loss, changes in mood or behavior (such as decreased sex drive, irritability, or forgetfulness), feeling cold, constipation, the voice gets deeper, urinating more often than usual, nausea or vomiting, and stomach area (abdomen) pain
• Problems in other organs–signs and symptoms may include severe muscle weakness, numbness or tingling in hands or feet, confusion, blurry vision, double vision, or other vision problems, changes in mood or behavior, extreme sensitivity to light, neck stiffness, eye pain or redness, skin blisters or peeling, chest pain, irregular heartbeat, shortness of breath, or swelling of the ankles
• Severe infections–signs and symptoms of infection may include fever, cough, flu-like symptoms, pain when urinating, and frequent urination or back pain
• Severe infusion reactions–signs and symptoms of infusion reactions may include chills or shaking, itching or rash, flushing, shortness of breath or wheezing, swelling of your face or lips, dizziness, fever, feeling like passing out, and back or neck pain

Getting medical treatment right away may help keep these problems from becoming more serious. A healthcare provider may treat patients with corticosteroid or hormone replacement medicines. A healthcare provider may delay or completely stop treatment with Tecentriq if patients have severe side effects.

Before receiving Tecentriq, patients should tell their healthcare provider about all of their medical conditions, including if they:

• have immune system problems (such as Crohn’s disease, ulcerative colitis, or lupus); have had an organ transplant; have lung or breathing problems; have liver problems; have a condition that affects the nervous system (such as myasthenia gravis or Guillain-Barre syndrome); or are being treated for an infection
• are pregnant or plan to become pregnant. Tecentriq can harm an unborn baby. Patients should tell their healthcare provider right away if they become pregnant or think they may be pregnant during treatment with Tecentriq. Females who are able to become pregnant:
  • A healthcare provider should do a pregnancy test before they start treatment with Tecentriq.
  • They should use an effective method of birth control during their treatment and for at least 5 months after the last dose of Tecentriq.
• are breastfeeding or plan to breastfeed. It is not known if Tecentriq passes into the breast milk. Patients should not breastfeed during treatment and for at least 5 months after the last dose of Tecentriq

Patients should tell their healthcare provider about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

The most common side effects of Tecentriq when used alone include:

• feeling tired or weak
• nausea
• constipation
• cough
• shortness of breath
• decreased appetite

The most common side effects of Tecentriq when used in lung cancer with other anti-cancer medicines include:

• feeling tired or weak
• hair loss
• nausea
• diarrhea
• constipation
• decreased appetite

The most common side effects of Tecentriq when used with paclitaxel protein-bound include:

• hair loss
• feeling tired
• tingling or numbness in hands and feet
• nausea
• diarrhea
• low red blood cells (anemia)
• constipation
• cough
• headache
• low white blood cells
• decreased appetite
• vomiting

Tecentriq may cause fertility problems in females, which may affect the ability to have children. Patients should talk to their healthcare provider if they have concerns about fertility.

These are not all the possible side effects of Tecentriq. Patients should ask their healthcare provider or pharmacist for more information. Patients should call their doctor for medical advice about side effects.

Report side effects to the FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch.
Report side effects to Genentech at 1-888-835-2555.

Please visit http://www.Tecentriq.com for the Tecentriq full Prescribing Information for additional Important Safety Information.

About Perjeta

Perjeta is a medicine that targets the HER2 receptor, a protein found on the outside of many normal cells and in high quantities on the outside of cancer cells in HER2-positive cancers. Perjeta is designed specifically to prevent the HER2 receptor from pairing (or ‘dimerizing’) with other HER receptors (EGFR/HER1, HER3 and HER4) on the surface of cells, a process that is believed to play a role in tumor growth and survival. Binding of Perjeta to HER2 may also signal the body’s immune system to destroy the cancer cells. The mechanisms of action of Perjeta and Herceptin are believed to complement each other, as both bind to the HER2 receptor, but to different places. The combination of Perjeta and Herceptin is thought to provide a more comprehensive, dual blockade of HER signaling pathways, thus preventing tumor cell growth and survival.

Perjeta Indication Statements

Perjeta (pertuzumab) is approved for use in combination with Herceptin (trastuzumab) and docetaxel in people who have HER2-positive breast cancer that has spread to different parts of the body (metastatic) and who have not received anti-HER2 therapy or chemotherapy for metastatic breast cancer.

Perjeta (pertuzumab) is approved for use in combination with Herceptin (trastuzumab) and chemotherapy for:

• use prior to surgery (neoadjuvant treatment) in people with HER2-positive, locally advanced, inflammatory, or early stage breast cancer (tumor is greater than two centimeters in diameter or node-positive). Perjeta should be used as part of a complete treatment regimen for early breast cancer.
• use after surgery (adjuvant treatment) in people with HER2-positive early breast cancer that has a high likelihood of coming back.

Important Safety Information

Side effects with Perjeta

• Not all people have serious side effects; however, side effects with Perjeta therapy are common. It is important for patients to know what side effects may happen and what symptoms patients should watch for.
• A patient’s doctor may stop treatment if serious side effects happen. Patients should be sure to contact their healthcare team right away if they have questions or are worried about any side effects.

Most serious side effects of Perjeta

Perjeta may cause heart problems, including those without symptoms (such as reduced heart function) and those with symptoms (such as congestive heart failure).

• A patient’s doctor may run tests to monitor the patient’s heart function before and during treatment with Perjeta.
• Based on test results, a patient’s doctor may hold or discontinue treatment with Perjeta.
• Patients should contact a health care professional immediately for any of the following: new onset or worsening shortness of breath, cough, swelling of the ankles/legs, swelling of the face, palpitations, weight gain of more than five pounds in 24 hours, dizziness or loss of consciousness.
• Receiving Perjeta during pregnancy can result in the death of an unborn baby and birth defects.
• Birth control should be used while receiving Perjeta and for seven months after a patient’s last dose of Perjeta. If a patient is a mother who is breastfeeding, she should talk with her doctor about either stopping breastfeeding or stopping Perjeta.
• If a patient thinks she may be pregnant, she should contact her healthcare provider immediately.
• If a patient is exposed to Perjeta during pregnancy, or becomes pregnant while receiving Perjeta or within seven months following her last dose of Perjeta in combination with Herceptin, she is encouraged to report Perjeta exposure to Genentech at (888) 835-2555.

Other possible serious side effects

• Perjeta should not be used in patients who are allergic to pertuzumab or to any of the ingredients in Perjeta.
• Infusion-related reactions: Perjeta is a medicine that is delivered into a vein through a needle. Perjeta has been associated with infusion-related reactions, some fatal. The most common infusion-related reactions when receiving Perjeta, Herceptin and docetaxel were feeling tired, abnormal or altered taste, allergic reactions, muscle pain and vomiting. The most common infusion-related reactions when receiving Perjeta alone were fever, chills, feeling tired, headache, weakness, allergic reactions and vomiting.
• Severe allergic reactions: Some people receiving Perjeta may have severe allergic reactions, called hypersensitivity reactions or anaphylaxis, which may happen quickly and may affect many areas of the body. Severe allergic reactions, some fatal, have been observed in patients treated with Perjeta.

Most common side effects

The most common side effects of Perjeta when given with Herceptin and docetaxel for treatment of breast cancer that has spread to other parts of the body (metastatic) are:

• Diarrhea
• Hair loss
• Low levels of white blood cells with or without fever
• Nausea
• Feeling tired
• Rash
• Damage to the nerves (numbness, tingling, pain in hands/feet)

The most common side effects of Perjeta when given with Herceptin and chemotherapy as part of an early breast cancer regimen before surgery are:

• Constipation
• Damage to the nerves (numbness, tingling, pain in hands/feet)
• Diarrhea
• Feeling tired
• Hair loss
• Headache
• Low levels of red blood cells
• Low levels of white blood cells with or without fever
• Low platelet count
• Mouth blisters or sores
• Nausea
• Pain in the muscles
• Vomiting
• Weakness

Side effects may vary based on chemotherapy regimen.

The most common side effects of Perjeta when given with Herceptin and chemotherapy as part of an early breast cancer regimen after surgery are:

• Diarrhea
• Nausea
• Hair loss
• Feeling tired
• Damage to the nerves (numbness, tingling, pain in hands/feet)
• Vomiting

Patients are encouraged to report side effects to Genentech and the FDA. Report side effects to the FDA at (800) FDA-1088 or http://www.fda.gov/medwatch. Report side effects to Genentech at (888) 835-2555.

Please see the Perjeta full Prescribing Information for additional Important Safety Information, including most serious side effects, at http://www.perjeta.com.

Herceptin Indication Statements

Adjuvant Breast Cancer

Herceptin is approved for the treatment of early stage breast cancer that is Human Epidermal growth factor Receptor 2-positive (HER2-positive) and has spread into the lymph nodes, or is HER2-positive and has not spread into the lymph nodes. If it has not spread into the lymph nodes, the cancer needs to be estrogen receptor/progesterone receptor (ER/PR)-negative or have one high-risk feature.* Herceptin can be used in several different ways:

• As part of a treatment course including the chemotherapy drugs doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel. This treatment course is known as “AC→TH.”
• With the chemotherapy drugs docetaxel and carboplatin. This treatment course is known as “TCH.”
• Alone after treatment with multiple other therapies, including an anthracycline (doxorubicin)-based therapy (a type of chemotherapy).

Patients are selected for therapy based on an FDA-approved test for Herceptin.

*High risk is defined as ER/PR-positive with one of the following features: tumor size greater than 2 cm, age less than 35 years, or tumor grade 2 or 3.

Metastatic Breast Cancer

Herceptin has two approved uses in metastatic breast cancer:

• Herceptin in combination with the chemotherapy drug paclitaxel is approved for the first-line treatment of Human Epidermal growth factor Receptor 2-positive (HER2-positive) metastatic breast cancer.
• Herceptin alone is approved for the treatment of HER2-positive breast cancer in patients who have received one or more chemotherapy courses for metastatic disease.

Patients are selected for therapy based on an FDA-approved test for Herceptin.

Important Safety Information

Possible serious side effects with Herceptin

Not all people have serious side effects, but side effects with Herceptin therapy are common. 

Although some people may have a life-threatening side effect, most do not.

A patient’s doctor will stop treatment if any serious side effects occur.

Herceptin is not for everyone. A patient should be sure to contact their doctor if they are experiencing any of the following:

HEART PROBLEMS

These include heart problems—such as congestive heart failure or reduced heart function—with or without symptoms. The risk for and seriousness of these heart problems were highest in people who received both Herceptin and a certain type of chemotherapy (anthracycline). In a study of adjuvant (early) breast cancer, one patient died of significantly weakened heart muscle. A patient’s doctor will check for signs of heart problems before, during, and after treatment with Herceptin.

INFUSION REACTIONS, including:

• Fever and chills
• Feeling sick to your stomach (nausea)
• Throwing up (vomiting)
• Pain (in some cases at tumor sites)
• Headache
• Dizziness
• Shortness of breath

These signs usually happen within 24 hours after receiving Herceptin.

A patient should be sure to contact their doctor if they:

Are a woman who could become pregnant, or may be pregnant

Herceptin may result in the death of an unborn baby or birth defects. Contraception should be used while receiving Herceptin and for seven months after a patient's last dose of Herceptin. If a patient is or becomes pregnant while receiving Herceptin or within seven months after their last dose of Herceptin, the patient should immediately report Herceptin exposure to Genentech at (888) 835-2555. 

Have any signs of SEVERE LUNG PROBLEMS, including:

• Severe shortness of breath
• Fluid in or around the lungs
• Weakening of the valve between the heart and the lungs
• Not enough oxygen in the body
• Swelling of the lungs
• Scarring of the lungs

A patient’s doctor may check for signs of severe lung problems when he or she examines the patient.

Have LOW WHITE BLOOD CELL COUNTS

Low white blood cell counts can be life threatening. Low white blood cell counts were seen more often in patients receiving Herceptin plus chemotherapy than in patients receiving chemotherapy alone.

A patient’s doctor may check for signs of low white blood cell counts when he or she examines the patient.

Side effects seen most often with Herceptin

Some patients receiving Herceptin for breast cancer had the following side effects:

• Fever
• Feeling sick to your stomach (nausea)
• Throwing up (vomiting)
• Infusion reactions
• Diarrhea
• Infections
• Increased cough
• Headache
• Feeling tired
• Shortness of breath
• Rash
• Low white and red blood cell counts
• Muscle pain

A patient should contact their doctor immediately if they have any of the side effects listed above.

Patients are encouraged to report side effects to Genentech and the FDA. Report side effects to the FDA at (800) FDA-1088 or http://www.fda.gov/medwatch. Report side effects to Genentech at (888) 835-2555.

Please see the Herceptin full Prescribing Information for additional Important Safety Information, including most serious side effects, at http://www.herceptin.com.

Avastin Indications:

• Metastatic colorectal cancer (mCRC) for first- or second-line treatment in combination with intravenous 5-fluorouracil–based chemotherapy. It is also approved to treat mCRC for second-line treatment, when used with fluoropyrimidine-based (combined with irinotecan or oxaliplatin) chemotherapy, after cancer progresses following a first-line treatment that includes Avastin.
  • Avastin is not approved for use after the primary treatment of colon cancer that has not spread to other parts of the body
• Advanced nonsquamous non–small cell lung cancer (NSCLC) in combination with carboplatin and paclitaxel, in people who have not received chemotherapy for their advanced disease
• Metastatic kidney cancer (mRCC) when used with interferon alfa
• Glioblastoma (GBM) in adult patients whose cancer has progressed after prior treatment (recurrent or rGBM)
• Advanced cervical cancer (CC) in combination with paclitaxel and cisplatin or paclitaxel and topotecan, is approved to treat persistent, recurrent, or metastatic cancer of the cervix
• Ovarian cancer (OC). Avastin, in combination with carboplatin and paclitaxel, followed by Avastin alone, is used for the treatment of patients with advanced (Stage III or IV) epithelial ovarian, fallopian tube, or primary peritoneal cancer following initial surgery.

Avastin in combination with paclitaxel, pegylated liposomal doxorubicin or topotecan, is approved to treat platinum-resistant recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer (prOC) in women who received no more than two prior chemotherapy treatments.

Avastin, either in combination with carboplatin and paclitaxel or with carboplatin and gemcitabine, followed by Avastin alone, is approved for the treatment of patients with platinum-sensitive recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer (psOC)

Possible serious side effects

Everyone reacts differently to Avastin therapy. So, it’s important to know what the side effects are. Although some people may have a life-threatening side effect, most do not . Their doctor will stop treatment if any serious side effects occur. Patients should contact their health care team if there are any signs of these side effects.

Most serious side effects (not common, but sometimes fatal):

• GI perforation. A hole that develops in the stomach or intestine. Symptoms include pain in the abdomen, nausea, vomiting, constipation, or fever
• Wounds that don’t heal. A cut made during surgery can be slow to heal or may not fully heal. Avastin should not be used for at least 28 days before or after surgery and until surgical wounds are fully healed
• Serious bleeding. This includes vomiting or coughing up blood; bleeding in the stomach, brain, or spinal cord; nosebleeds; and vaginal bleeding. If a patient has recently coughed up blood or had serious bleeding, they should be sure to tell their doctor

Other possible serious side effects

• Abnormal passage in the body. This type of passage—known as a fistula—is an irregular connection from one part of the body to another and can sometimes be fatal
• Severe high blood pressure. Blood pressure that severely spikes or shows signs of affecting the brain. Blood pressure should be monitored every 2 to 3 weeks while on Avastin and after stopping treatment
• Kidney problems. These may be caused by too much protein in the urine and can sometimes be fatal
• Infusion reactions. These were uncommon with the first dose (less than 3% of patients). 0.2% of patients had severe reactions. Infusion reactions include high blood pressure or severe high blood pressure that may lead to stroke, trouble breathing, decreased oxygen in red blood cells, a serious allergic reaction, chest pain, headache, tremors, and excessive sweating. The patient’s doctor or nurse will monitor for signs of infusion reactions
• Severe stroke or heart problems. These may include blood clots, mini-stroke, heart attack, chest pain, and the heart may become too weak to pump blood to other parts of the body (congestive heart failure). These can sometimes be fatal
• Nervous system and vision problems. Signs include headache, seizure, high blood pressure, sluggishness, confusion, and blindness

Side effects seen most often

In clinical studies across different types of cancer, some patients experienced the following side effects:

• High blood pressure
• Too much protein in the urine
• Nosebleeds
• Rectal bleeding
• Back pain
• Headache
• Taste change
• Dry skin
• Inflammation of the skin
• Inflammation of the nose
• Watery eyes

Avastin is not for everyone

Patients should talk to their doctor if they are:

• Undergoing surgery. Avastin should not be used for 28 days before or after surgery and until surgical wounds are fully healed
• Pregnant or think they are pregnant. Data have shown that Avastin may harm a woman’s unborn baby. Birth control should be used while patients are on Avastin. If Avastin is stopped, patients should keep using birth control for 6 months before trying to become pregnant
• Planning to become pregnant. Taking Avastin could cause a woman’s ovaries to stop working and may impair her ability to have children
• Breastfeeding. Breastfeeding while on Avastin may harm the baby and is therefore not recommended during and for 6 months after taking Avastin

Patients should talk with their doctor if they have any questions about their condition or treatment.

Report side effects to the FDA at (800) FDA-1088 or http://www.fda.gov/medwatch.

Report side effects to Genentech at (888) 835-2555.

For full Prescribing Information and Boxed WARNINGS on Avastin please visit http://www.avastin.com.

About Genentech

Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.

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