In patients with resected stage II-IIIA non-small cell lung cancer (NSCLC), atezolizumab showed a disease-free survival benefit versus best supporting care after adjuvant chemotherapy, with pronounced benefit in the subgroup whose tumors expressed PD-L1 on 1% or more of tumor cells, and no new safety signals, according to a study published in The Lancet.
In a randomized, multicenter, open-label, phase III study (IMpower010), researchers evaluated adjuvant atezolizumab versus best supportive care following adjuvant platinum-based chemotherapy in patients at 227 sites in 22 countries and regions. Eligible patients were aged 18 or older with completely resected stage IB (tumors ≥4 cm) to IIIA NSCLC per the Union Internationale Contre le Cancer and American Joint Committee on Cancer staging system (7th edition). Patients were randomly assigned (1:1) by a permuted-block method (block size of four) to receive adjuvant atezolizumab (1,200 mg every 21 days; for 16 cycles or 1 year) or best supportive care (observation and regular scans for disease recurrence) after adjuvant platinum-based chemotherapy (one to four cycles).
Atezolizumab Improved Disease-Free SurvivalThe primary endpoint—investigator-assessed disease-free survival—was tested hierarchically first in the stage II-IIIA population subgroup whose tumors expressed PD-L1 on 1% or more of tumor cells, then all patients in the stage II-IIIA population, and finally, an intention-to-treat (ITT) population (stage IB-IIIA). Safety was evaluated in all patients who were randomly assigned and received atezolizumab or best supportive care. Between October 7, 2015 and September 19, 2018, 1,280 patients were enrolled after complete resection; 1,269 received adjuvant chemotherapy, of whom 1,005 were eligible for randomization to atezolizumab (n = 507) or best supportive care (n = 498); 495 in each group received treatment.
The researchers found that after a median follow-up of 32.2 months, atezolizumab treatment improved disease-free survival compared with best supportive care in patients in the stage II-IIIA population whose tumors expressed PD-L1 on 1% or more of tumor cells (HR, 0.66; 95% CI, 0.50-0.88) and in all patients in the stage II-IIIA population (HR, 0.79; 95% CI, 0.64-0.96). “We showed an improved disease-free survival with atezolizumab in PD-L1-expressing stage II–IIIA NSCLC and in all randomly assigned patients with stage II–IIIA disease across most disease stages, in patients with nodal involvement, and across most surgery types and chemotherapy regimens,” said study co-author Nassar Altorki, MD, of New York-Presbyterian Hospital, Weill Cornell Medicine.
In the ITT population, the HR for disease-free survival was 0.81 (95% CI, 0.67-0.99). Atezolizumab-related grade 3 and 4 adverse events occurred in 53 (11%) of 495 patients and grade 5 events in four patients (1%).
“Novel adjuvant strategies are needed to optimize outcomes after complete surgical resection in patients with early-stage NSCLC,” the study authors concluded. “Atezolizumab after adjuvant chemotherapy offers a promising treatment option for patients with resected early-stage NSCLC.”