OS Benefit Seen in Nonsquamous NSCLC With Triplet Regimen in IMpower130

Federico Cappuzzo, MD

Results from the phase III IMpower130 trial demonstrated a statistically significant improvement in both progression-free survival (PFS) and overall survival (OS) with atezolizumab (Tecentriq), carboplatin, and nab-paclitaxel (Abraxane) compared with chemotherapy alone in patients with previously untreated stage IV nonsquamous non—small cell lung cancer (NSCLC).

“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, during the 2018 ESMO Congress.

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 withEGFR/ALKabnormalities. 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 theEGFR/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.

Reference:

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.

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