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

Federico Cappuzzo, MD

The first-line triplet of atezolizumab (Tecentriq), carboplatin, and nab-paclitaxel (Abraxane) was associated with a statistically significant improvement in both progression-free and overall survival (OS) compared with chemotherapy alone in patients with stage IV nonsquamous non—small cell lung cancer (NSCLC), according to results from the phase III IMpower130 trial presented at the 2018 ESMO Congress.

“The IMpower130 results support atezolizumab plus chemotherapy as a treatment option for patients with advanced nonsquamous NSCLC, irrespective of PD-L1 status,” said Federico Cappuzzo, MD, director of medical oncology and of the Department of Hematology and Oncology at the Azienda Unità Sanitaria Locale della Romagna-Ravenna in Italy.

IMpower130 is a multicenter, open-label, randomized phase III study investigating atezolizumab plus carboplatin/nab-paclitaxel compared with carboplatin/nab-paclitaxel alone in chemotherapy-naïve patients with stage IV nonsquamous NSCLC with measurable disease.

Patients were randomized 2:1 to receive the atezolizumab triplet as induction therapy followed by maintenance atezolizumab, or chemotherapy alone followed by best supportive care or pemetrexed every 3 weeks as maintenance. Atezolizumab was administered until investigator-assessed loss of clinical benefit or toxicity, while chemotherapy was given until progressive disease or toxicity. Stratification factors included gender, baseline liver metastases, and PD-L1 expression.

There were 723 patients in the intent-to-treat (ITT) population and 679 patients in the ITT—wild-type (WT) population, which excluded patients with EGFR/ALK abnormalities. The co-primary endpoints were investigator-assessed PFS and OS in the ITT-WT cohort; secondary endpoints were OS and PFS in the ITT group, as well as PD-L1 expression, ORR, and safety.

Results showed that, in the ITT-WT population, the median PFS with the atezolizumab regimen was 7.0 months (95% CI, 6.2-7.3) and 5.5 months (95% CI, 4.4-5.9) for carboplatin/nab-paclitaxel alone (HR, 0.64; 95% CI, 0.54-0.77; P <.0001). The 6- and 12-month PFS rates also favored the atezolizumab arm at 56.1% and 29.1% versus 42.5% and 14.1% with chemotherapy.

The atezolizumab arm was also superior in OS in the ITT-WT population, with a median of 18.6 months (95% CI, 16.0-21.2) versus 13.9 months (95% CI, 12.0-18.7) with carboplatin/nab-paclitaxel alone (HR, 0.79; 95% CI, 0.64-0.98; P = .033). The 1- and 2-year OS rates with atezolizumab were 63.1% and 39.6% versus 55.5% and 30.0% in the carboplatin/nab-paclitaxel arm.

ORR and median DOR was 49.2% and 8.4 months (6.9-11.8) with the atezolizumab regimen versus 31.9% and 6.1 months (5.5-7.9) with chemotherapy (P = .0004). In the atezolizumab arm, the ORR consisted of a 2.5% complete response rate, 46.8% partial response rate, 30.4% stable disease rate, and 11% progressive disease rate. Responses were ongoing in 36.8% of patients on atezolizumab and 19.4% on chemotherapy.

The PFS benefit was observed across all prespecified subgroups, except for those with liver metastases (HR, 0.93; 95% CI, 0.59-1.47); this group also did not experience an OS benefit (HR, 1.04; 95% CI, 0.63-1.72).

Investigator-assessed PFS and OSS in the ITT population were similar to the ITT-WT population, with a median PFS of 7.0 months for atezolizumab and 5.6 months for carboplatin/nab-paclitaxel (HR, 0.65; 95% CI, 0.54-0.77; P <.0001). The 6- and 12-month PFS rates were 56.4% and 28.9% with atezolizumab and 42.9% and 14.2% for chemotherapy.

The median OS for the ITT group for atezolizumab and chemotherapy was 18.1 months and 13.9 months, respectively (HR, 0.80; 95% CI, 0.65-0.99; P = .039). Additionally, the 1- and 2-year OS rates in this group were 62.7% and 39.3% on the atezolizumab arm and 55.1% and 29.9% with carboplatin/nab-paclitaxel.

The PFS and OS benefits varied in the EGFR/ALK-positive subgroups; the median PFS was 7.0 months and 6.0 months with atezolizumab and carboplatin/nab-paclitaxel alone (HR, 0.75; 95% CI 0.36-1.54), respectively; median OS was 14.4 months and 10.0 months (HR, 0.98; 95% CI, 0.41-2.31).

PFS data were also reported by levels of high, low, and negative PD-L1 expression: high (6.4 vs 4.6 months; HR, 0.51; 95% CI, 0.34-0.77), low (8.3 vs 6.0 months; HR, 0.61; 95% CI, 0.43-0.85), and negative (6.2 vs 4.7 months; HR, 0.72; 0.56-0.91). For OS, the benefit was similar: high (17.3 vs 16.9 months; HR, 0.84; 95% CI, 0.51-1.39), low (23.7 vs 15.9 months; HR, 0.70; 95% CI, 0.45-1.08) and negative (15.2 vs 12.0 months; HR, 0.81; 95% CI, 0.61-1.08).

In the ITT-WT population, 39% of patients on the atezolizumab arm received subsequent therapy compared with 66.2% on carboplatin/paclitaxel; moreover, 40.8% of patients on chemotherapy crossed over to receive atezolizumab.

All-grade adverse events (AEs) were comparable between the 2 arms, while grade 3/4 treatment-related AEs (TRAEs) were seen in 73.2% and 60.3% of those on atezolizumab and chemotherapy alone, respectively. Grade 3/4 AEs of special interest on atezolizumab included colitis (n = 5), hypothyroidism (n = 3), hepatitis (n = 2), and diabetes mellitus (n = 2).

Serious grade 3/4 TRAEs were doubled in the atezolizumab arm at 23.7% versus 12.9%, and AEs leading to dose interruptions occurred in 85.0% and 80.2% of patients.

“Atezolizumab plus chemotherapy had a safety profile consisted with adverse events associated with single-agent therapy—no new safety signals were identified,” concluded Cappuzzo.

Cappuzzo F, McCleod M, Hussein M, et al. IMpower130: progression-free survival (PFS) and safety analysis from a randomised phase 3 study of carboplatin + nab-paclitaxel (CnP) with or without atezolizumab (atezo) as first-line (1L) therapy in advanced non-squamous NSCLC. Presented at: 2018 ESMO Congress; October 19-23, 2018; Munich, Germany. Abstract LBA53.

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