Frontline Atezolizumab Regimen Improves Survival in NSCLC

Sandra Horning, MD

Treatment with the combination of atezolizumab (Tecentriq), bevacizumab (Avastin), carboplatin, and paclitaxel significantly improved overall survival (OS) compared with bevacizumab and chemotherapy alone for patients with advanced nonsquamous non—small cell lung cancer (NSCLC), according to findings from the phase III IMpower150 trial.¹

The OS benefit was observed across predetermined patient subgroups, including cohorts with varying PD-L1 expression levels, according to Genentech (Roche), the manufacturer of atezolizumab and bevacizumab. The toxicity profile for the combination was consistent with previous data for the drugs as single agents, with no new safety signals.

A third arm of the trial—atezolizumab plus carboplatin and paclitaxel—did not demonstrate a significant OS improvement at the interim analysis versus bevacizumab and chemotherapy, and the study is now continuing to the final analysis. Genentech plans to submit the latest IMpower150 findings for presentation 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,” Sandra Horning, MD, chief medical officer and head of Global Product Development at Roche, said in a statement.

“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,” added Horning.

Previously reported data from IMpower150 showed that the combination of atezolizumab, bevacizumab, carboplatin, and paclitaxel delayed progression or death by 38% compared with bevacizumab and chemotherapy alone for patients with advanced nonsquamous NSCLC.²

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

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

The median age of patients in the trial was 63 years and 60% were previous smokers. Overall, most patients were male and the ECOG performance status was 0 for 39% of patients in arm B and for 43% in arm C. The minimum follow-up at the time of the analysis was 9.5 months. For the interim analysis, the study was only designed to compare arms B and C.

The objective response rate (ORR) in the atezolizumab arm was 64% compared with 48% in the bevacizumab/chemotherapy alone group. PD-L1 expression on immune and tumor cells did not appear to impact efficacy, as those testing negative for the marker still experienced an improvement in PFS with atezolizumab (HR, 0.77; 95% CI, 0.61-0.99). However, there was a 50% reduction 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).

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

Each of the agents showed similar toxicity profiles as in previous trials. Serious treatment-related adverse events were observed in 25.4% of patients treated with the atezolizumab regimen compared with 19.3% of those in the control arm. There were no new safety signals or toxicity issues with this combination.

Atezolizumab is currently approved as a treatment for patients with metastatic NSCLC following progression on a platinum-containing regimen, and an FDA-approved targeted therapy for those patients harboring EGFR or ALK abnormalities. For lung cancer, bevacizumab is approved for patients with nonsquamous NSCLC in combination with carboplatin and paclitaxel.

References

1. Phase III IMpower150 Study Showed Genentech’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 +/− bevacizumab, with or without atezolizumab in 1L non-squamous metastatic NSCLC (IMpower150). Annals of Oncology, 2017;28(11). Abstract LBA1_PR.

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The IMpower150 study enrolled 1202 patients with stage IV nonsquamous NSCLC. Patients were randomized evenly to receive 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 EGFR or ALK alterations were excluded from the study. Patients were also tested for a tumor T-effector gene expression signature.