Atezolizumab Plus Chemo Improves PFS in Frontline Squamous NSCLC

Sandra Horning, MD

The addition of atezolizumab (Tecentriq) to frontline carboplatin and nab-paclitaxel (Abraxane) delayed progression or death compared with chemotherapy alone for patients with advanced squamous non—small cell lung cancer (NSCLC), according to topline findings from the phase III IMpower131 trial released by Genentech (Roche), the manufacturer of the anti–PD-L1 agent.

The coprimary endpoints for the IMpower131 study were progression-free survival (PFS) and overall survival (OS). A statistically significant OS improvement was not observed at the interim analysis and the study is now continuing according to its design. No new safety signals emerged with the atezolizumab combination. Roche reported that the findings will be submitted for presentation at an upcoming oncology meeting.

“Squamous non-small cell lung cancer is difficult to treat and there have been limited new treatment options over the last few decades,” Sandra Horning, MD, chief medical officer and head of Global Product Development at Roche, said in a statement. “We will share the IMpower131 results with global health authorities and we look forward to seeing more mature overall survival data.”

The multicenter, open-label phase III IMpower131 study randomized 1021 chemotherapy-naïve patients with stage IV squamous NSCLC to upfront treatment with atezolizumab, carboplatin, and paclitaxel (arm A); atezolizumab, carboplatin, and nab-paclitaxel (arm B); or the control arm of carboplatin and nab-paclitaxel (arm C).

For arm A, the induction phase comprised 4 or 6 cycles of atezolizumab plus carboplatin and paclitaxel, administered on day 1 of each 21-day cycle. Patients then received maintenance atezolizumab every 3 weeks as long as a clinical benefit continued to occur and there was no disease progression.

The induction phase for arm B involved 4 to 6 cycles of atezolizumab, carboplatin, and nab-paclitaxel. Patients received atezolizumab and carboplatin on day 1 of each 21-day cycle. This was followed by the same maintenance atezolizumab regimen as in arm A.

For arm C, induction comprised 4 or 6 cycles of carboplatin and nab-paclitaxel. Patients received carboplatin on day 1 of each 21-day cycle, and nab-paclitaxel was administered on days 1, 8, and 15 of each 21-day cycle. The maintenance phase consisted of best supportive care.

Previously reported results from a phase Ib trial presented at the 2015 World Conference on Lung Cancer demonstrated the promise of combining frontline atezolizumab with chemotherapy in patients with metastatic NSCLC.¹ Patients received atezolizumab at a dose of 15 mg/kg IV every 3 weeks in addition to 1 of 3 chemotherapy doublets: carboplatin paired with paclitaxel, pemetrexed (nonsquamous histology only), or nab-paclitaxel. Treatment continued for 4 to 6 cycles, followed by atezolizumab maintenance therapy until disease progression (and optionally, pemetrexed maintenance in that arm of the trial).

The primary outcome was overall response rate, as determined by RECIST criteria. Data were reported for 58 patients, 41 of whom were evaluable for response. The patients had a median age of 65, and 79% of the cohort had nonsquamous histology.

Overall, 26 (63.4%) of the 41 evaluable patients met the criteria for objective response. Four of 8 (50%) patients in the atezolizumab plus carboplatin/paclitaxel cohort achieved objective responses (all partial responses). The combination of atezolizumab, carboplatin, and pemetrexed induced a response in 13 (76.5%) of 17 patients (all partial responses). Responses also occurred in 9 (56%) of 16 patients who received carboplatin and nab-paclitaxel in addition to atezolizumab.

Data from the phase III IMpower150 trial reported in December at the ESMO Immuno Oncology Congress showed that the frontline combination of atezolizumab (Tecentriq), bevacizumab (Avastin), 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 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 a preliminary examination of OS, there was a 22.5% reduction in the risk of death with the atezolizumab combination compared with bevacizumab and chemotherapy alone. After a minimum follow-up of 9.5 months, the median OS was 14.4 (95% CI, 12.8-17.1) versus 19.2 months (95% CI, 16.8-26.1), in favor of the atezolizumab group (HR, 0.775; 95% CI, 0.619-0.970; P = .0262). The next OS analysis will take place in the first half of 2018.

References

1. Camidge R, Liu SV, Powderly J, et al. Atezolizumab (MPDL3280A) combined with platinum-based chemotherapy in non—small cell lung cancer (NSCLC): a phase Ib safety and efficacy update. Presented at: 16th World Conference on Lung Cancer; September 6-9; Denver, CO. Abstract 02.07.
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 current analysis was only a comparison of arm B versus arm C. The study design stipulates that the nab-paclitaxel arm (B) must first demonstrate a statistically significant OS benefit versus the control arm (C) before the paclitaxel arm (A) can be compared with the control arm for PFS and OS.