Study Finds Survival Benefit With Upfront Atezolizumab Combo for NSCLC

Sandra Horning, MD

Sandra Horning, MD

According to findings from the phase III IMpower150 trial,¹significant improvement was found in overall survival (OS) with a treatment regimen of atezolizumab (Tecentriq), bevacizumab (Avastin), carboplatin, and paclitaxel compared to the combination of bevacizumab and chemotherapy alone for patients with advanced nonsquamous non—small cell lung cancer (NSCLC).

OS benefit was found across the predetermined patient subgroups, which included subgroups of cohorts with varying PD-L1 expression levels, according to Genentech (Roche), the manufacturer of atezolizumab and bevacizumab. Toxicity was consistent to previous data for the drugs as single agents and showed no new safety signals.

There was a third arm of the trial including the combination of atezolizumab plus carboplatin and paclitaxel. At interim analysis, this arm did not show a significant OS improvement compared to bevacizumab and chemotherapy. While the study is still continuing towards the final analysis, Genentech plans to submit the latest IMpower150 findings at an upcoming oncology meeting.

“We are pleased that the IMpower150 study demonstrated a clinically meaningful survival benefit for people receiving their initial treatment for this type of advanced lung cancer,” said Sandra Horning, MD, chief medical officer and head of Global Product Development at Roche. “These results add to the growing body of evidence supporting the role of combining Tecentriq with Avastin. We will submit these additional data to global health authorities and hope to bring this potential treatment option to patients as soon as possible."

Findings from IMpower150 announced prior to this presentation demonstrated delayed progression or death by 38% with the combination of atezolizumab, bevacizumab, carboplatin, and paclitaxel compared to bevacizumab and chemotherapy alone for patients with advanced nonsquamous NSCLC.²

A median progression-free survival (PFS) of 8.3 months was found in the atezolizumab regimen compared to a PFS of 6.8 months with bevacizumab and chemotherapy alone (HR, 0.62; 95% CI, 0.52-0.74;&nbsp;P<.0001). The 12-month PFS rate was 37% with the atezolizumab-containing regimen compared to an 18% rate with the bevacizumab and chemotherapy arm.

A total of 1202 patients with stage IV nonsquamous NSCLC&nbsp;were enrolled in the IMpower150 study. Randomized evenly, patients were given either atezolizumab plus carboplatin and paclitaxel (arm A), atezolizumab with bevacizumab plus carboplatin and paclitaxel (arm B), or bevacizumab plus carboplatin and paclitaxel (arm C). Those with known&nbsp;EGFRor&nbsp;ALKalterations were excluded from the study. Patients were also tested for a tumor T-effector gene expression signature.

Atezolizumab was administered in the investigational arm at 1200 mg intravenously every 3 weeks and bevacizumab was given at 15 mg/kg. Each arm recieved carboplatin and paclitaxel on day 1 of each cycle for 4 to 6 cycles. Maintenance therapy was given for arm A with atezolizumab alone while arm B patients received maintenance therapy with the combination of bevacizumab and atezolizumab. Patients in arm C recieved maintenance with bevacizumab alone.

Median age of patients was 63 years while 60% of the patients were previous smokers. Most patients in the trial were male. The ECOG performance status in arm B was 0 for 39% of patients and for 43% in arm C. There was a minimum follow-up of 9.5 months at the time of the analysis. Interim analysis was only designed to look at arms B and C.

An objective response rate (ORR) of 64% was found in the atezolizumab arm and an ORR of&nbsp;48% in the bevacizumab/chemotherapy alone group. PD-L1 expression on immune and tumor cells didn't seem to affect efficacy; those testing negative for the marker still experienced an improvement in PFS with atezolizumab (HR, 0.77; 95% CI, 0.61-0.99). However, a 50% reduction was found in the risk of progression or death with atezolizumab in those testing positive for PD-L1 on immune and tumor cells (IHC1/2/3; HR, 0.50; 95% CI, 0.39-0.64).

The addition of atezolizumab reduced the risk of progression or death by 49% in the T-effector signature wild-type population. Median PFS was 11.3 months with the PD-L1 inhibitor compared to 6.8 months with bevacizumab/chemotherapy alone (HR, 0.51; 95% CI, 0.38-0.68;P<.0001). In this group, there was an ORR of 69% with atezolizumab versus 54% without the PD-L1 inhibitor. The 12-month PFS rate was 18% with bevacizumab/chemotherapy compared to 46% with the addition of atezolizumab.

Similar toxicity profiles were identified in each of the agents, as in previous trials. In patients treated with the atezolizumab regimen, 25.4% experienced serious treatment-related adverse events versus 19.3% in the control arm. No new safety signals or toxicity issues were found with this combination.

For patients with metastatic NSCLC, atezolizumab is currently approved as a treatment following progression on a platinum-containing regimen. It is also an FDA-approved targeted therapy for those patients withEGFRor&nbsp;ALKabnormalities. For patients with nonsquamous NSCLC, bevacizumab is approved&nbsp;in combination with carboplatin and paclitaxel.

References:

1. Phase III IMpower150 Study Showed Genentech&rsquo;s TECENTRIQ (Atezolizumab) and Avastin (Bevacizumab) Plus Carboplatin and Paclitaxel Helped People With Advanced Lung Cancer Live Longer Compared to Avastin Plus Carboplatin and Paclitaxel. Genentech. Posted March 25, 2018. Accessed March 26, 2018. https://bit.ly/2IUPqG2.
2. Reck M. Primary PFS and safety analyses of a randomized Phase III study of carboplatin + paclitaxel +/&minus; bevacizumab, with or without atezolizumab in 1L non-squamous metastatic NSCLC (IMpower150).Ann Oncol.2017;28(11). Abstract LBA1_PR.