Adding perioperative atezolizumab to platinum-based chemotherapy nearly doubled median event-free survival (EFS) in patients with stage IIB-IIIB resectable non-small cell lung cancer (NSCLC) without EGFR or ALK alterations, but the improvement did not reach statistical significance in the final analysis of the phase 3 IMpower030 trial.

The unusually strong outcomes in the control group may help explain why the primary endpoint did not reach statistical significance, said study investigator Benjamin Solomon, MD, of Peter MacCallum Cancer Centre in Melbourne, Australia, in a presentation at the World Conference on Lung Cancer (WCLC) 2026. The placebo group in this study performed “better than historic controls from similar studies,” he explained.

Still, the findings showed “clinically meaningful” numerical improvements across several important outcomes, including median EFS and overall survival, and “further support the role of perioperative immunotherapy for patients with resectable NSCLC,” Solomon added in a conference statement.

Testing the Perioperative Strategy

Several trials have shown that perioperative chemoimmunotherapy can improve outcomes in patients with NSCLC, and one — CheckMate 816 — found that a neoadjuvant-only strategy can also improve outcomes.

However, the role of atezolizumab remains less clear. In resectable NSCLC, atezolizumab is currently approved in the adjuvant setting. Previous findings from IMpower010 found that adjuvant atezolizumab reduced the risk for disease recurrence but was not associated with a significant improvement in overall survival in patients with resected stage II-IIIA NSCLC with PD-L1 expression on ≥ 1% of tumor cells after platinum-based chemotherapy.

The IMpower030 trial aimed to explore whether extending atezolizumab across both sides of surgery could improve outcomes, though did not include neoadjuvant- or adjuvant-only treatment arms.

The study enrolled patients with resectable stage II to selected stage IIIB NSCLC without EGFR or ALK alterations who were eligible for curative resection. Patients were randomized to four cycles of platinum-based chemotherapy plus atezolizumab 1200 mg or placebo every 3 weeks. A total of 397 patients were included in the stage IIB-IIIB wild-type population and 440 patients in the intent-to-treat (ITT) wild-type population. After surgery, patients in the atezolizumab group received up to 16 additional cycles, whereas the control group received best supportive care. Nearly 90% of patients in both groups proceeded to curative surgery.

The primary endpoint was independent review facility-assessed EFS in patients with stage IIB-IIIB disease.

The researchers found that median EFS in the stage IIB-IIIB wild-type population was nearly twofold higher in the atezolizumab group — 62.8 months with atezolizumab plus chemotherapy compared with 34.9 months with chemotherapy alone — after a median follow-up of 69.3 months, but the benefit was not statistically significant (hazard ratio [HR], 0.77; 95% CI, 0.58-1.02; P = .07).

In the ITT wild-type population, median EFS was 67.2 months with atezolizumab vs 43.9 months with placebo (HR, 0.75; 95% CI, 0.57-0.98).

Perioperative atezolizumab led to higher pathologic complete response (pCR) rates (29.6% vs 8.5%) and major pathologic response rates (53.6% vs 24.4%) in the stage IIB-IIIB wild-type population, based on independent review. Similarly, in the ITT wild-type population, the corresponding pCR and major pathologic response rates were higher in the atezolizumab arm — 30.6% vs 8.6%, and 54.3% vs 24.9%, respectively.

Other secondary endpoints favored perioperative atezolizumab, including investigator-assessed EFS, disease-free survival, and overall survival.

In the ITT wild-type population, median overall survival was not reached in the atezolizumab arm compared with 81.7 months in the placebo group (HR, 0.77; 95% CI, 0.57-1.05). At 5 years, 66.0% of patients in the atezolizumab group and 59.4% in the placebo group were alive.

Among patients who achieved R0 resection, the median disease-free survival was 82.7 months with atezolizumab compared with 54.5 months with placebo (HR, 0.67; 95% CI, 0.49-0.90).

Higher rates of adverse events occurred in the neoadjuvant phase in both arms. Grade 3-4 and grade 5 adverse events occurred in 58% and 3.1% of patients receiving neoadjuvant atezolizumab vs 63.4% and 1.3% with placebo. In the adjuvant phase, the corresponding grade 3-4 and grade 5 adverse event rates were 5.3% and 2.2% vs 1.8% and 0.4%.

Solomon noted that the placebo group performed better than historical controls from perioperative immunotherapy studies, possibly reflecting differences in patient selection. Compared with historical control populations, the IMpower030 control group had a lower surgery cancellation rate (11% vs 19%-22%), higher pCR and major pathologic response rates, and longer median EFS and better median overall survival (81.7 vs 53.2-73.7 months).

Study discussant Anne-Marie Dingemans, MD, PhD, who was not involved in the research, similarly highlighted the “striking” outcomes in the IMpower030 control group. Dingemans of Erasmus Medical Center in Rotterdam, Netherlands, suggested that the strong outcomes in the control group may have reflected the trial’s selection of patients who were considered resectable. The trial required upfront confirmation by a thoracic surgeon or multidisciplinary team that patients were candidates for curative R0 resection.

Dingemans also explained that, since “we know that event-free survival is driven by pCR and PD-L1 status,” analyses stratified by pCR and PD-L1 status would help interpret the findings.

The study was sponsored by F. Hoffmann-La Roche. Disclosures for study authors are available with the original study materials. Dingemans reported receiving consultant fees from Amgen, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, Janssen Pharmaceuticals, Pfizer, and Sanofi; and serving on data and safety monitoring committees for Bayer and F. Hoffmann-La Roche.