Combination of Atezolizumab, Bevacizumab Improves Lung Cancer Survival

Patients with advanced non-squamous non-small cell lung cancer (NSCLC) who were initially treated with the combination of atezolizumab (Tecentriq) and bevacizumab (Avastin) plus carboplatin and paclitaxel lived significantly longer than those initially treated with bevacizumab plus carboplatin and paclitaxel, according to a Genentech press release.

Treating patients with the combination of atezolizumab and bevacizumab plus carboplatin and paclitaxel resulted in a 38% reduction in the risk of disease worsening or death compared with bevacizumab plus carboplatin and paclitaxel. This reduction was observed in all key subgroups, including those with differing PD-L1 expression levels.

The open-label, randomized and controlled phase 3 study tested the reaction of azetolizumab with carboplatin and paclitaxel, with and without the combination of bevacizumab, according to the release.

The study included 1202 patients with stage 4 non-squamous NSCLC who were not previously treated with chemotherapy and who did not have ALK and EGFR mutations.

The trial was divided into 3 groups, with the first receiving azetolizumab plus carboplatin and paclitaxel (arm A), the second receiving azetolizumab combined with bevacizumab plus carboplatin and paclitaxel (arm B), and the third control group receiving bevacizumab plus carboplatin and paclitaxel (arm C).

Patients in arm A were intravenously administered 1200-mg of azetolizumab with intravenous infusions of carboplatin and paclitaxel on day 1 of a 3-week treatment cycle. Patients underwent 4 or 6 treatment cycles total. Patients in arm B received 1200 mg of azetolizumab and 15mg/kg of bevacizumab intravenously, combined with infusions of carboplatin and paclitaxel on day 1 of a 3-week treatment cycle, with 4 or 6 cycles of treatment.

Individuals in arm C received 15mg/kg of bevacizumab intravenously, combined with carboplatin and paclitaxel infusions on day 1 of a 3-week treatment cycle, with 4 or 6 total cycles.

All patients received maintenance treatment after the cycles until the loss of clinical benefit or disease progression was reached.

Azetolizumab and bevacizumab were most effective when combined, according to the release. Bevacizumab has anti-angiogenic properties that deprive a tumor of its blood supply and prevent it from growing and spreading. It also enhances the efficacy of azetolizumab, which binds with PD-L1 on tumor cells and prevents it from interacting with other receptors, resulting in the reactivation of immune cells.

Both individual drugs have possible adverse effects, but no new events were determined from the combination of azetolizumab and bevacizumab, according to the release.

Possible side effects of azetolizumab include pneumonitis, hepatitis, colitis, hormonal gland problems, complications of the nervous system, eye inflammation, heart problems, severe infections, and infusion reactions. Patients should reconsider taking azetolizumab if they have immune system problems, have had an organ transplant, have a condition of the lungs, liver, or nervous system, are being treated for an infection, are pregnant or planning to become pregnant, or are breastfeeding. Patients are advised to wait 5 months after treatment to become pregnant or breastfeed.

Other side effects include feeling tired, decreased appetite, shortness of breath, cough, nausea, muscle or bone pain, or constipation.

Bevacizumab could have fatal side effects for patients, including gastrointestinal perforation, wounds that will not heal, serious bleeding, fistulas, severe high blood pressure, kidney complications, infusion reactions, stroke or heart attack, or nervous system and vision complications. Patients are advised not to take bevacizumab if they are planning on having surgery, pregnant or planning on becoming pregnant, and breastfeeding.

Other common adverse effects include high blood pressure, high levels of protein in the urine, nosebleeds, rectal bleeding, back pain, headache, taste change, dry skin, inflammation of the skin and nose, or watery eyes.

Genentech said the study demonstrates a need for further research on the combination of azetolizumab and bevacizumab for a variety of cancers, including NSCLC.