Adding Tecentriq (atezolizumab) to a combination of Avastin (bevacizumab) and chemotherapy cut the risk of death by nearly half in a group of metastatic non-small cell lung cancer (NSCLC) patients with liver metastasis, an exploratory Phase 3 trial analysis shows.
The findings were presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, in Chicago, in a poster titled, “IMpower150: Analysis of efficacy in patients with liver metastases.”
Genentech‘s Tecentriq is a kind of immunotherapy called an immune checkpoint inhibitor, which blocks signals from cancer cells that prevent immune cells from properly eliminating the cancer. Specifically, Tecentriq targets the PD-L1 protein and prevents it from binding to the PD-1 receptor on immune cells, thereby restoring immune surveillance.
Tecentriq is approved in the U.S., in combination with Avastin (bevacizumab) and the chemotherapies Taxol (paclitaxel) and carboplatin, for the first-line treatment of metastatic non-squamous NSCLC patients without EGFR or ALK mutations in their tumors.
The approval was based on positive results from IMpower150 (NCT02366143), a multicenter, open-label, randomized Phase 3 trial that compared a combination of Tecentriq plus Taxol and carboplatin, with or without Avastin, to a combination of Avastin, Taxol, and carboplatin.
Avastin, by Roche, is a human antibody that binds the VEGF protein, an important protein in blood vessel formation. By blocking VEGF-mediated signaling, Avastin disrupts the tumor’s blood supply, preventing its growth and spread.
The trial included in 1,202 patients with metastatic non-squamous NSCLC not previously treated with chemotherapy. It showed that Tecentriq in combination with Avastin and chemotherapy extended the lives of patients without EGFR or ALK mutations to 19.2 months compared with 14.7 months for patients on Avastin and chemotherapy.
The combination also reduced the risk of disease worsening or death by 29%, and led to better response rates (55%) than the Avastin-chemo combination (42%). Responses were also longer in the Tecentriq group (a median of 10.8 months versus 6.5 months for the Avastin combination).
At the ASCO meeting, researchers reported new findings from the group of 162 patients whose cancer had spread to the liver at the time they entered the trial. Liver metastasis affects nearly one-fifth of NSCLC patients and are associated with a particularly poor prognosis.
After a minimum follow-up of 20 months, the patients receiving a combination of Tecentriq plus Avastin and chemotherapy had a significant survival advantage, living a median of 13.3 months compared with 9.4 months among those receiving the Avastin-chemo combination. This meant that Tecetriq reduced their risk of death by 48%.
The Tecentriq combination also reduced the risk of disease worsening or death by 59%, and shrank tumors in 60.8% of patients compared with 41.1% receiving Avastin plus chemotherapy. Responses were also longer with Tecentriq — 10.7 months versus 4.6 months.
The researchers had already reported that the safety of the Tecentriq combo in the overall population of IMpower150 matched that of its individual components. The findings were similar for those with liver metastasis, with a similar proportion of patients in both groups experiencing severe or life-threatening adverse events — 52% versus 55% in the control arm.
“We are pleased to present further positive results from the Phase 3 IMpower150 study that show benefit in people with baseline liver metastases, a population with a worse prognosis for survival,” Sandra Horning, MD, Roche’s chief medical officer and head of global product development, said in a press release.
“Initial treatment with Tecentriq, Avastin and chemotherapy may represent an important new option for people with baseline liver metastases, as their risk of death was reduced by nearly half and 60% responded to the combination treatment,” Horning added.
Tecentriq is also approved in the U.S. for second-line treatment of metastatic NSCLC for patients who fail to respond to platinum-based chemotherapy.