Atezolizumab/Bevacizumab Combo Improves PFS for Untreated Advanced NSCLC

Sandra Horning, MD

The addition of atezolizumab (Tecentriq) to bevacizumab (Avastin), carboplatin, and paclitaxel delayed progression or death compared with bevacizumab and chemotherapy alone for patients with advanced non-squamous non—small cell lung cancer (NSCLC), according to topline findings from the phase III IMpower150 trial released by Roche, the manufacturer of the anti–PD-L1 and anti–VEGF agents.

UPDATE 3/26/2018: Frontline Atezolizumab Regimen Improves Survival in NSCLC

The co-primary endpoints for the IMpower150 study were progression-free survival (PFS) and overall survival (OS). Although exact numbers have not yet been released, Roche called the reduction in progression or death with the addition of atezolizumab a "clinically meaningful reduction." At the interim analysis, data for OS were not yet mature, with the company labeling the findings as "encouraging."

Data from the interim analysis of the IMpower150 study are being presented in December 2017 at the ESMO Immuno Oncology Congress, Roche said in a release. Additionally, the company has already initiated discussions with the FDA and EMA regarding regulatory approval.

“We are extremely encouraged by these results and will submit these data to health authorities globally with the goal of bringing a potential new standard of care for the initial treatment of lung cancer,” Sandra Horning, MD, Roche’s chief medical officer and Head of Global Product Development, said in a statement. “In addition to first-line NSCLC, we are testing the ability of Tecentriq and Avastin to enhance the potential of the immune system to combat a broad range of other cancers.”

The IMpower150 study enrolled 1202 patients with stage IV non-squamous 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.

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.

Atezolizumab is currently approved as a treatment for patients with metastatic NSCLC following progression on a platinum-containing regimen. This indication was based on findings from the phase III OAK trial,¹ which compared the PD-L1 inhibitor with docetaxel. This trial included 1225 patients with locally advanced or metastatic NSCLC—regardless of histology or PD-L1 status—who progressed during or after platinum-containing chemotherapy.

In the study, the median PFS was similar between arms, at 2.8 months with atezolizumab versus 4.0 months for docetaxel (HR, 0.95; 95% CI, 0.82-1.10). The median OS with atezolizumab was 13.8 months compared with 9.6 months for docetaxel (HR, 0.73; 95% CI, 0.62-0.87). The benefit in OS was similar between histologies, with an HR of 0.73 in the non-squamous population (95% CI, 0.60-0.89).

Additionally, data from the phase II POPLAR study also supported the approval.² This phase II trial enrolled 287 patients with advanced NSCLC following frontline chemotherapy. The median PFS was 2.7 months with atezolizumab and 3.0 months for docetaxel (HR, 0.94; 95% CI, 0.72-1.23). Median OS was 9.7 versus 12.6 months, for docetaxel and atezolizumab, respectively (HR, 0.73; 95% CI, 0.53-0.99). In the non-squamous group, the OS was 15.5 months for atezolizumab versus 10.9 months with docetaxel (HR, 0.69; 95% CI, 0.47-1.01).

For lung cancer, bevacizumab is approved for patients with non-squamous NSCLC in combination with carboplatin and paclitaxel. In the 878-patient study that was pivotal for the approval,³ the combination of bevacizumab and chemotherapy showed a median OS of 12.3 months compared with 10.3 months for chemotherapy alone (HR, 0.80; 95% CI, 0.68-0.94; P = .013). The median PFS was 6.2 months with bevacizumab versus 4.5 months for chemotherapy alone (HR, 0.66; 95% CI, 0.57-0.77; P <.001).

Several studies continue to assess atezolizumab as a treatment for patients with lung cancer as part of various combinations or as monotherapy. The PD-L1 inhibitor is being looked at with nab-paclitaxel (Abraxane) and in combinations with pemetrexed and other chemotherapy agents. The combination of atezolizumab and bevacizumab is being assessed in several solid tumors, with promising findings presented in renal cell carcinoma. Trial looking at this combination are currently ongoing.

References:

1. Rittmeyer A, Barlesi F, Waterkamp D, et al. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet. 2017;389(10066).
2. Fehrenbacher L, Spira A, Ballinger M, et al. Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet. 2017;387(10030).
3. Avastin Prescribing Information. Genentech, Inc. December 2016.

For the interim analysis, the study was only designed to compare arms B and C. In addition to the co-primary endpoints, the study also assed objective response rates and safety. The company noted there were no unexpected adverse events in the study and that each of the agents showed similar toxicity profiles as in other trials.