On January 18, 2023 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported that the Phase III IMbrave050 study met its primary endpoint of recurrence-free survival (RFS) at the prespecified interim analysis (Press release, Genentech, JAN 18, 2023, View Source [SID1234626349]). The study is evaluating Tecentriq (atezolizumab) in combination with Avastin (bevacizumab) as adjuvant treatment following surgery for people with early-stage hepatocellular carcinoma (HCC) at high risk of disease recurrence. The Tecentriq combination showed a statistically significant improvement in RFS in the intention-to-treat population of HCC patients who have an increased risk of recurrence following resection or ablation with curative intent, compared with active surveillance.
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Overall survival data were immature at the time of interim analysis and follow-up will continue to the next analysis. Safety for Tecentriq and Avastin was consistent with the known safety profile of each therapeutic agent and with the underlying disease. Results from the IMbrave050 study will be discussed with health authorities, including the U.S. Food and Drug Administration and the European Medicines Agency, and presented at an upcoming medical meeting.
"Today, more than 70% of people with early-stage HCC may have their cancer return after surgery, which is associated with poorer prognosis and shorter survival. IMbrave050 is the first Phase III study to show that a cancer immunotherapy combination reduced the risk of disease returning in people with this type of HCC," said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. "We are excited by the clinical benefit that this adjuvant Tecentriq combination may bring to people with early liver cancer and look forward to seeing more mature data to further confirm the benefit."
With liver cancer incidence increasing and mortality rates rising globally, effective treatments are urgently required. Genentech is working in partnership with the community and leveraging its diagnostic and pharmaceutical expertise to develop solutions for patients that address unmet needs at each stage of liver cancer. IMbrave050 is part of Genentech’s overall commitment to drive fundamental treatment change and improve outcomes for people living with liver cancer. In unresectable HCC (uHCC), for example, Tecentriq plus Avastin was the first treatment in over a decade to significantly improve overall survival over the existing standard of care, based on data from the IMbrave150 study. The Tecentriq combination quickly became a standard of care in uHCC and is clearly defined as a preferred front-line treatment in multiple international clinical guidelines.
Genentech has an extensive development program for Tecentriq, including multiple ongoing and planned Phase III studies across different lung, genitourinary, skin, breast, gastrointestinal, gynecological, and head and neck cancers. This includes studies evaluating Tecentriq both alone and in combination with other medicines, as well as studies in metastatic, adjuvant and neoadjuvant settings across various tumor types.
About the IMbrave050 study
IMbrave050 is a Phase III global, multicenter, open-label, randomized study evaluating the efficacy and safety of adjuvant Tecentriq plus Avastin, compared with active surveillance, in people with HCC at high risk of recurrence (determined by the size and number of cancerous lesions and the histopathology results, if available) after surgical resection or ablation with curative intent.
The study randomized 662 people with a ratio of 1:1 to receive either Tecentriq (1,200 mg every three weeks) plus Avastin (15 mg/kg every three weeks) for a maximum of 12 months, or no intervention with active surveillance. The primary endpoint is independent review facility-assessed RFS. Key secondary endpoints include overall survival, RFS as determined by the investigator and RFS in patients with PD-L1-positive disease.
About hepatocellular carcinoma
According to the American Cancer Society, it is estimated that nearly 42,000 Americans were diagnosed with liver cancer in 2022. Liver cancer incidence has more than tripled since 1980. Nine out of ten cases of HCC are caused by chronic liver disease, which includes chronic hepatitis B and C infection, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), alcohol-related liver disease (ALD) and cirrhosis resulting from these conditions.
If diagnosed in the early stage, surgery may be prescribed to remove the primary tumor, however an estimated 70-80% of people with early-stage HCC experience disease recurrence following surgery. Early recurrence is associated with poorer prognosis and shorter survival. Tumor size, number of tumors, and portal vein invasion are associated with an increased risk of recurrence.
About Tecentriq (atezolizumab)
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.
About Avastin (bevacizumab)
Avastin is a prescription-only medicine that is a solution for intravenous infusion. It is a biologic antibody designed to specifically bind to a protein called VEGF that plays an important role throughout the lifecycle of the tumor to develop and maintain blood vessels, a process known as angiogenesis. Avastin is designed to interfere with the tumor blood supply by directly binding to the VEGF protein to prevent interactions with receptors on blood vessel cells. The tumor blood supply is thought to be critical to a tumor’s ability to grow and spread in the body (metastasize).
Tecentriq U.S. Indications
Tecentriq is a prescription medicine used to treat:
Adults with a type of lung cancer called non-small cell lung cancer (NSCLC).
Tecentriq may be used alone as a treatment for their lung cancer:
to help prevent their lung cancer from coming back after their tumor(s) has been removed by surgery and they have received platinum-based chemotherapy, and
they have stage 2 to 3A NSCLC (patients should talk to their healthcare provider about what these stages mean), and
their cancer tests positive for "PD-L1."
Tecentriq may be used alone as their first treatment when their lung cancer:
has spread or grown, and
their cancer tests positive for "high PD-L1," and
their tumor does not have an abnormal "EGFR" or "ALK" gene.
Tecentriq may be used with the medicines bevacizumab, paclitaxel, and carboplatin as their first treatment when their lung cancer:
has spread or grown, and
is a type called "non-squamous NSCLC," and
their tumor does not have an abnormal "EGFR" or "ALK" gene.
Tecentriq may be used with the medicines paclitaxel protein-bound and carboplatin as their first treatment when their lung cancer:
has spread or grown, and
is a type called "non-squamous NSCLC," and
their tumor does not have an abnormal "EGFR" or "ALK" gene.
Tecentriq may be used alone when their lung cancer:
has spread or grown, and
if they have tried chemotherapy that contains platinum, and it did not work or is no longer working.
if their tumor has an abnormal "EGFR" or "ALK" gene, they should have also tried an FDA-approved therapy for tumors with these abnormal genes, and it did not work or is no longer working.
Adults with a type of lung cancer called small cell lung cancer (SCLC). Tecentriq may be used with the chemotherapy medicines carboplatin and etoposide as their first treatment when their lung cancer:
is a type called "extensive-stage small cell lung cancer," which means that it has spread or grown.
Adults with a type of liver cancer called hepatocellular carcinoma (HCC). Tecentriq may be used with the medicine bevacizumab when their liver cancer:
has spread or cannot be removed by surgery, and
they have not received other medicines by mouth or injection through their vein (IV) to treat their cancer.
Adults with a type of skin cancer called melanoma. Tecentriq may be used with the medicines cobimetinib and vemurafenib in patients with melanoma when their skin cancer:
has spread to other parts of the body or cannot be removed by surgery, and
has a certain type of abnormal "BRAF" gene. Healthcare providers will perform a test to make sure this Tecentriq combination is right for the patient.
Adults and children 2 years of age and older with a type of soft tissue tumor (cancer) called alveolar soft part sarcoma (ASPS). Tecentriq may be used when your sarcoma:
has spread to other parts of the body or cannot be removed by surgery.
It is not known if Tecentriq is safe and effective when used:
in children younger than 2 years of age for the treatment of ASPS.
in children for the treatment of NSCLC, SCLC, HCC or melanoma.
Important Safety Information
What is the most important information about Tecentriq?
Tecentriq can cause the immune system to attack normal organs and tissues in any area of the body and can affect the way they work. These problems can sometimes become severe or life threatening and can lead to death. Patients can have more than one of these problems at the same time. These problems may happen anytime during their treatment or even after their treatment has ended.
Patients should call or see their healthcare provider right away if they develop any new or worse signs or symptoms, including:
Lung problems
cough
shortness of breath
chest pain
Intestinal problems
diarrhea (loose stools) or more frequent bowel movements than usual
stools that are black, tarry, sticky, or have blood or mucus
severe stomach-area (abdomen) pain or tenderness
Liver problems
yellowing of the skin or the whites of the eyes
severe nausea or vomiting
pain on the right side of their stomach area (abdomen)
dark urine (tea colored)
bleeding or bruising more easily than normal
Hormone gland problems
headaches that will not go away or unusual headaches
eye sensitivity to light
eye problems
rapid heartbeat
increased sweating
extreme tiredness
weight gain or weight loss
feeling more hungry or thirsty than usual
urinating more often than usual
hair loss
feeling cold
constipation
their voice gets deeper
dizziness or fainting
changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness
Kidney problems
decrease in their amount of urine
blood in their urine
swelling of their ankles
loss of appetite
Skin problems
rash
itching
skin blistering or peeling
painful sores or ulcers in mouth or nose, throat, or genital area
fever or flu-like symptoms
swollen lymph nodes
Problems can also happen in other organs.
These are not all of the signs and symptoms of immune system problems that can happen with Tecentriq. Patients should call or see their healthcare provider right away for any new or worse signs or symptoms, including:
Chest pain, irregular heartbeat, shortness of breath, or swelling of ankles
Confusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems, tingling or numbness of the arms or legs
Double vision, blurry vision, sensitivity to light, eye pain, changes in eyesight
Persistent or severe muscle pain or weakness, muscle cramps
Low red blood cells, bruising
Infusion reactions that can sometimes be severe or life-threatening. Signs and symptoms of infusion reactions may include:
chills or shaking
itching or rash
flushing
shortness of breath or wheezing
dizziness
feeling like passing out
fever
back or neck pain
Complications, including graft-versus-host disease (GVHD), in people who have received a bone marrow (stem cell) transplant that uses donor stem cells (allogeneic). These complications can be serious and can lead to death. These complications may happen if patients undergo transplantation either before or after being treated with Tecentriq. A healthcare provider will monitor for these complications.
Getting medical treatment right away may help keep these problems from becoming more serious. A healthcare provider will check patients for these problems during their treatment with Tecentriq. A healthcare provider may treat patients with corticosteroid or hormone replacement medicines. A healthcare provider may also need to 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 received an organ transplant
have received or plan to receive a stem cell transplant that uses donor stem cells (allogeneic)
have received radiation treatment to their chest area
have a condition that affects their nervous system, such as myasthenia gravis or Guillain-Barré syndrome
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
decreased appetite
nausea
cough
shortness of breath
The most common side effects of Tecentriq when used in lung cancer with other anti-cancer medicines include:
feeling tired or weak
nausea
hair loss
constipation
diarrhea
decreased appetite
The most common side effects of Tecentriq when used in hepatocellular carcinoma (HCC) with bevacizumab include:
high blood pressure
feeling tired or weak
too much protein in the urine
The most common side effects of Tecentriq when used in melanoma with cobimetinib and vemurafenib include:
skin rash
joint, muscle, or bone pain
feeling tired or weak
liver injury
fever
nausea
itching
swelling of legs or arms
mouth swelling (sometimes with sores)
low thyroid hormone levels
sunburn or sun sensitivity
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 about the benefits and side effects of Tecentriq.
Report side effects to the FDA at 1-800-FDA-1088 or View Source
Report side effects to Genentech at 1-888-835-2555.
Please see View Source for full Prescribing Information and additional Important Safety Information.
Avastin is approved for:
Avastin, in combination with atezolizumab, is indicated for the treatment of patients with unresectable or metastatic hepatocellular carcinoma (HCC) who have not received prior systemic therapy.
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.
GI perforation. A hole that develops in the stomach or intestine. Symptoms include pain in the abdomen, nausea, vomiting, constipation, or fever
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
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
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-related 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, therefore women should not breastfeed during and for 6 months after taking Avastin
Patients should talk with their doctor if they have any questions about their condition or treatment.