OS Benefit Seen With Atezolizumab Combination in PD-L1-High Squamous NSCLC

Federico Cappuzzo, MD

Federico Cappuzzo, MD

The combination of atezolizumab (Tecentriq) plus carboplatin and nab-paclitaxel (Abraxane) demonstrated a clinical overall survival (OS) benefit in a subgroup of patients with advanced squamous non—small cell lung cancer (NSCLC) and a high level of PD-L1 expression in the phase III IMpower131 trial. Final data for this study was presented at the 2019 World Conference on Lung Cancer (WCLC).¹

AmongPD-L1—high (TC3 or IC3) patients, the median OS was 23.4 months (95% CI, 17.8 – not evaluable) with the atezolizumab triplet compared to 10.2 months (95% CI, 7.1 – 17.5) in patients receiving carboplatin plus nab-paclitaxel alone (HR, 0.48; 95% CI, 0.29-0.81).

“In this specific subgroup of patients, we had a reduction in the risk of death of more than 50%,” said Federico Cappuzzo, MD, Azienda Unità Sanitaria Locale della Romagna, Ravenna/Italy. “A meaningful survival difference was observed in patients with strongly PD-L1—positive tumors, suggesting that they may benefit from combining carboplatin and nab-paclitaxel with atezolizumab.”

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 (n = 338), the induction phase comprised 4 or 6 cycles of atezolizumab (1200 mg) plus carboplatin (AUC 6) and paclitaxel (200 mg/m²), 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 (n = 343) involved 4 to 6 cycles of atezolizumab (1200 mg), carboplatin (AUC 6), and nab-paclitaxel (100 mg/m²). 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 (n = 340), induction comprised 4 or 6 cycles of carboplatin and nab-paclitaxel (100 mg/m²). 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.

The coprimary endpoints for the IMpower131 study were progression-free survival (PFS) and OS. The analysis presented at the WCLC was only a comparison of arm B versus arm C. The study design stipulated 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.

In the overall patient population, there was no OS benefit with the addition of atezolizumab. At a median follow-up of 25.5 months, the median OS was 14.2 months in the atezolizumab arm versus 13.5 months with chemotherapy alone (HR, 0.88; 95% CI, 0.73-1.05;P= .1581).

The trial did, however, meet its coprimary endpoint of PFS. At a median follow-up of 17.1 months, the median PFS was 6.3 months (95% CI, 5.7-7.1) with the addition of atezolizumab versus 5.6 months (95% CI, 5.6-5.7) with chemotherapy alone (HR, 0.71; 95% CI, 0.60-0.85;P = 0.0001).²The 12-month PFS rates were 24.7% versus 12.0%, respectively.

Regarding safety, grade 3/4 and serious treatment-related adverse events occurred in 68.0% versus 56.9% and 20.4% versus 10.5% of the atezolizumab and control arms, respectively.

References:

1. R. Jotte, F. Cappuzzo, I. Vynnychenko, et al. IMPOWER131: Final OS results of carboplatin + nab-paclitaxel ± atezolizumab in advanced squamous NSCLC. Presented at: IASLC 20th World Conference on Lung Cancer; September 7-10, 2019; Barcelona, Spain. Abstract OA14.02.
2. Jotte RM, Cappuzzo F, Vynnychenko I, et al. IMpower131: Primary PFS and safety analysis of a randomized phase III study of atezolizumab + carboplatin + paclitaxel or nab-paclitaxel vs carboplatin + nab-paclitaxel as 1L therapy in advanced squamous NSCLC.J Clin Oncol. 2018;36(18 suppl; abstr LBA9000). doi: 10.1200/JCO.2018.36.18_suppl.LBA9000.