Atezolizumab Plus Carboplatin/Nab-Paclitaxel Improves OS in Frontline NSCLC

Sandra Horning, MD

Adding atezolizumab (Tecentriq) to nab-paclitaxel (Abraxane) and carboplatin in the frontline setting significantly improved overall survival (OS) in patients with advanced non—small cell lung cancer (NSCLC), according to findings from the phase III IMpower130 study.

Atezolizumab also improved progression-free survival (PFS), the coprimary endpoint of the IMpower130 study, according to Genentech (Roche), the manufacturer of the PD-L1 inhibitor. The company plans to share the study data at an upcoming oncology meeting.

“The results of the IMpower130 study add to the growing evidence showing the clinical benefit of Tecentriq-based combinations in the treatment of advanced nonsquamous non—small cell lung cancer,” Sandra Horning, MD, chief medical officer and head of Global Product Development at Genentech, said in a statement. “We will share these results with global health authorities with the goal of bringing this potential treatment option to people with this disease.”

The multicenter, open-label IMpower130 study (NCT02367781) included 724 chemotherapy-naïve patients with stage IV nonsquamous NSCLC. Patients were randomized in a 1:1 ratio to receive nab-paclitaxel/carboplatin alone or combined with atezolizumab.

In the experimental arm, patients received atezolizumab and carboplatin on day 1, and nab-paclitaxel on days 1, 8, and 15 of each 21-day cycle for 4 or 6 cycles or until there was no longer a clinical benefit. Those with successful induction received maintenance atezolizumab until there was a lack of clinical benefit.

The comparator group received carboplatin on day 1 and nab-paclitaxel on days 1, 8, and 15 of each 21-day cycle for 4 or 6 cycles or until disease progression. Crossover to single-agent atezolizumab at progression was allowed. Those with successful induction received best supportive care during the maintenance phase. Additionally, switch maintenance to pemetrexed was allowed for patients who had given prior consent to a revised study protocol. These individuals could receive single agent pemetrexed within 6 weeks of day 1 of their last induction cycle.

The comprimary endpoints were OS and PFS in the intent-to-treat (ITT) wild-type (WT) population (ie, those without EGFR or ALK mutations). Genentech reported that there were no new safety signals at the data cutoff.

The FDA is reviewing a separate atezolizumab regimen for approval in the frontline nonsquamous NSCLC setting. Specifically, the supplemental biologics license application (sBLA) is for atezolizumab (Tecentriq) for use in combination with bevacizumab (Avastin), carboplatin, and paclitaxel for the first-line treatment of patients with metastatic nonsquamous NSCLC. The FDA is scheduled to make its decision on the sBLA by September 5, 2018.

The sBLA is based on findings from the phase III IMpower150 trial, in which the atezolizumab regimen demonstrated a median progression-free survival (PFS) of 8.3 months compared with 6.8 months with bevacizumab and chemotherapy alone. The difference translated into a 38% reduction in the hazard for progression or death (HR, 0.62; 95% CI, 0.52-0.74; P <.0001).¹

In data scheduled to be presented at the 2018 ASCO Annual Meeting, the atezolizumab combination also improved overall survival in the IMpower150 trial. In the ITT-WT population, the median OS was 19.2 months with atezolizumab compared with 14.7 months for patients receiving bevacizumab and chemotherapy alone (HR, 0.78; 95% CI, 0.64-0.96; P = .016).

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 primary ITT analysis. Patients were also tested for a tumor T-effector gene expression signature.

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. Follow-up is continuing for patients in the atezolizumab/chemotherapy arm (arm A), and results will be reported at a later date.

Investigators evaluated multiple biomarker assays as potential ways to enrich for PFS, including the T-effector gene signature and PD-L1 expression by the SP142 and SP263 assays. Patients also were screened for EGFR mutations and ALK rearrangements. Overall, the PFS benefit was virtually identical between the ITT group (HR, 0.62; n = 692) and biomarker-enriched population (HR, 0.62; n = 503)

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.

References

1. Kowanetz M, Socinski MA, Zou W, et al. IMpower150: Efficacy of atezolizumab plus bevacizumab and chemotherapy in 1L metastatic nonsquamous NSCLC across key subgroups. Presented at: 2018 AACR Annual Meeting; April 14-18, 2018; Chicago, Illinois. Abstract CT076.
2. Mark A. Socinski, Robert M. Jotte, Federico Cappuzzo Overall survival (OS) analysis of IMpower150, a randomized Ph 3 study of atezolizumab (atezo) + chemotherapy (chemo) ± bevacizumab (bev) vs chemo + bev in 1L nonsquamous (NSQ) NSCLC. J Clin Oncol 36, 2018 (suppl; abstr 9002).

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The 12-month PFS rate was 37% with the atezolizumab-containing regimen and 18% with the bevacizumab plus chemotherapy regimen. The objective response rate was 64% versus 48%, respectively.