Atezolizumab Regimen Improves PFS in Frontline Nonsquamous NSCLC

Vassiliki A.

Papadimitrakopoulou, MD

The addition of atezolizumab (Tecentriq) to carboplatin/cisplatin in the first-line setting and to pemetrexed as maintenance therapy significantly improved progression free survival (PFS) in patients with stage IV nonsquamous non—small cell lung cancer (NSCLC).

The combination reduced the risk of disease worsening or death by 40% compared with chemotherapy alone (7.6 vs 5.2 months; HR, 0.60; 95% CI, 0.49-0.72; P <.0001). Vassiliki A. Papadimitrakopoulou, MD, chief of the section of thoracic medical oncology at The University of Texas MD Anderson Cancer Center, presented the interim analysis results at the 19th World Conference on Lung Cancer.¹

The global, randomized, open-label, phase III IMpower132 study evaluated the efficacy and safety of frontline atezolizumab plus carboplatin/cisplatin and maintenance therapy with pemetrexed in 578 chemotherapy-nai&#776;ve patients with stage IV nonsquamous NSCLC, without EGFR or ALK genetic alteration.

Patients were randomized 1:1 to receive 4 or 6 cycles of:

• carboplatin area under the curve (AUC) 6 mg/mL/min or 75 mg/m² cisplatin plus 500 mg/m² pemetrexed every 3 weeks, followed by pemetrexed as maintenance therapy (arm B; n = 286); or
• carboplatin/pemetrexed or cisplatin/pemetrexed plus 1200 mg of atezolizumab, followed by pemetrexed plus atezolizumab as maintenance therapy (arm A; n = 292).

Investigator-assessed PFS and overall survival (OS) served as the coprimary endpoints. Secondary endpoints included investigator-assessed objective response rate (ORR) and duration or response (DOR), patient-reported outcomes, and safety measures.

The majority of patients in arms A and B were younger than age 65 (median age, 64 vs 63, respectively), white (66.1% vs 71%), had an ECOG performance status of 0 (43.2% vs 40.1%), and were current or former smokers (87.3% vs 89.5%, respectively).

After a median follow-up of 14.8 months, those treated with atezolizumab demonstrated superior PFS, which was associated with a 40 percent reduction in the risk for progression in all patients and across key clinical subgroups, including Asian patients (HR, 0.42; 95% CI, 0.28-0.63), never smokers (HR, 0.49; 95% CI, 0.28-0.87), and current and former smokers (HR, 0.61; 95% CI, 0.50-0.74).

The atezolizumab arm also demonstrated superior 6-month PFS (59.1% vs 40.9%); 12-month PFS (33.7% vs 17%); ORR (47% vs 32%), including complete (2% vs 1%) and partial (45% vs 32%) responses; median DOR (10.1 vs 7.2 months); and ongoing response rates (42% vs 30%).

Further, the atezolizumab regimen improved OS by 4.5 months over pemetrexed-based chemotherapy alone (18.1 vs 13.6 months; HR, 0.81; 95% CI, 0.64-1.03; P = .0797); however, the difference was not statistically significant and Papadimitrakopoulou noted that the data will not be finalized until next year.

The investigators also conducted an exploratory analysis of clinical and biomarker subgroups, from which tissue was available from 60% of patients.

Among PD-L1—high patients in the atezolizumab cohort (n = 25) and the pemetrexed-based chemotherapy alone cohort (n = 20), median PFS was 10.8 months compared with 6.5 months, respectively (HR, 0.46; 95% CI, 0.22-0.96). Similarly, among PD-L1–low patients in both groups (n = 63 and 73, respectively), median PFS was 6.2 months versus 5.7 months (HR, 0.80; 95% CI, 0.56-1.16). Lastly, for those with PD-L1–negative disease in both arms (n = 88 and 75, respectively), median PFS was superior among those who received atezolizumab (8.5 vs 4.9 months; HR, 0.45; 95% CI, 0.31-0.64).

The safety profiled for the atezolizumab combinations appeared consistent with each individual therapy, and no new safety signals were identified. Grade 3/4 treatment-related adverse events (TRAEs) occurred in 53.6% of patients in arm A compared with 39.1% of those in arm B.

The most common AEs in arms A and B included rash (24% vs 21%, respecitvely), hypothyroidism (8% vs 2%), pneumonitis (6% vs 2%), hepatitis (5% vs 1%), infusion-related reactions (3% vs 1%), hyperthyroidism (2% vs 1%), severe cutaneous adverse reaction (1% vs 1%), pancreatitis (1% vs 1%), and colitis (1% vs 0%).

“The findings from IMpower132 indicate that the addition of atezolizumab to a backbone of carboplatin and pemetrexed chemotherapy provides better clinical efficacy than carboplatin and pemetrexed alone,” Papadimitrakopoulou said in a statement. “By inhibiting the interaction of PD-L1 with its receptors PD-1 and B7.1, atezolizumab restores tumor-specific T-cell immunity, offering a valuable treatment option that prolongs survival for patients with stage IV nonsquamous NSCLC.”

The final analysis is anticipated in the first half of 2019, she added.

Papadimitrakopoulou V, Cobo M, Bordoni R, et al. IMpower132: PFS and Safety Results with 1L Atezolizumab + Carboplatin/Cisplatin + Pemetrexed in Stage IV Non-Squamous NSCLC. Presented at: the IASLC 19th World Conference on Lung Cancer; September 23-26; Toronto, Canada. Abstract OA05.07.