FDA Approves Adjuvant Atezolizumab for PD-L1+ Non–Small Cell Lung Cancer
Atezolizumab is now approved for the adjuvant treatment of NCSLC expressing PD-L1≥1%. The approval is based on the IMpower010 study.
The FDA has granted approval to atezolizumab (Tecentriq) as adjuvant treatment following surgery and platinum-based chemotherapy for people with non-small cell lung cancer (NSCLC) whose tumors express PD-L1≥1%, as determined by an FDA-approved test, according to a press release from Genentech.1
Positive findings from the phase 2 IMpower010 study (NCT02486718) support the FDA’s decision. The study showed that adjuvant atezolizumab achieved disease-free survival (DFS) improvement in patients with early-stage resected NSCLC per investigator assessment, achieving the primary end point of the study.1,2
In the IMpower010 study 1280 patients with completely resected tumors, stage IB-IIIA disease, and an ECOG performance status 0-1 were included. Of those patients, 1269 patients were treated with up to four 21-day cycles of cisplatin-based chemotherapy in combination with pemetrexed, docetaxel, gemcitabine, or vinorelbine. Patients were subsequently randomized 1:1 to receive either adjuvant atezolizumab administered at 1200 mg every 3 weeks for up to 16 cycles or best supportive care (BSC).2,3
“The magnitude of benefit, particularly in patients with tumors with PD-L1 expression of at least 50% were really striking, Heather Wakelee, professor of Medicine at Sanford Health Care told Targeted Oncology, in an interview.
Secondary end points in the study included overall survival (OS), the percentage of patients who are disease-free at the 3-year and 5-year time points, DFS within selected populations, the number of patients with adverse events (AEs), the percentage of participants with anti-therapeutic antibodies to atezolizumab, the maximum plasma concentration of atezolizumab, and minimum serum concentration of atezolizumab.
Results showed that at a median follow-up was 32.2 months in the ITT population, the 24-month DFS rate was 74.6% in the atezolizumab arm compared with 60.0% in the BSC arm. At 36-months, the DFS rate was 61.0% with adjuvant atezolizumab compared with 48.2%. The median DFS was not evaluable (NE, 95% CI, 36.1-NE) in the atezolizumab arm versus 35.3 months (95% CI, 29.0-NE) in the BSC arm (stratified HR, 0.66; 95% CI, 0.50-0.88; P =.0004).
Evaluation of DFS across subgroup populations showed that most groups favored adjuvant atezolizumab over BSC, especially patients with PD-L1 expression. Those with an SP263 PD-L1 status ≥ 50% benefitted from adjuvant atezolizumab over BSC (HR, 0.43; 95% CI, 0.27-0.65), as did those with a status of ≥ 1% (HR, 0.66; 95% CI, 0.49-0.87), and those with a status of <1% (HR, 0.97; 95% CI, 0.72-1.31).
Those who tested positive for ALK rearrangement, however, favored BSC over atezolizumab (HR, 1.04; 95% CI, 0.38-2.90), and those who had never smoked (HR, 1.13; 95% CI, 0.77-1.67).
OS data were immature at the time of the analysis, but there was a trend toward OS improvement identified in the subgroups of patients with ≥ 1% PD-L1 expression (HR, 0.77; 95% CI, 0.;51-1.77).
The safety analysis of atezolizumab versus BSC showed consistency with the known safety profile. No new safety signals were observed in the study. In the adjuvant atezolizumab arm, 92.7% of patients experienced AEs of any grade compared with 70.7% of the BSC arm. AEs were grade 3 to 4 in severity for 21.8% of the atezolizumab arm compared with 11.5% of the control arm. Further, treatment with atezolizumab also led to treatment-related grade 3/4 AEs in 10.7% of patients. Serious AEs were occurred in 17.6% of the atezolizumab arm compared with 8.5% of the control arm, and grade 5 AEs occurred in 8 patients and 3 patients, respectively.
“Oncologists have a lot of experience managing immune related toxicity given the extensive use of these agents in many metastatic cancers. Oncologists need to stay alert for any potential immune mediated toxicity and treat accordingly with steroids or other interventions,” Wakelee stated, in the interview.
