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

Jason M. Broderick @jasoncology
Published: Tuesday, May 29, 2018

Dr. Sandra Horning
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.

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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