Atezolizumab fails primary endpoint in IMpower030 trial for resectable lung cancer

The phase 3 IMpower030 trial evaluating perioperative atezolizumab for resectable non-small cell lung cancer missed its primary endpoint of statistically significant event-free survival. Although the atezolizumab group nearly doubled median event-free survival to 62.8 months compared to 34.9 months for the placebo group, the result was not statistically significant. Investigators attribute this to the control group performing exceptionally well compared to historical controls, likely due to strict patient selection.

IMpower030 trial primary endpoint

• ▪The phase 3 IMpower030 trial evaluating perioperative atezolizumab plus platinum-based chemotherapy in patients with stage IIB-IIIB resectable non-small cell lung cancer (NSCLC) missed its primary endpoint of statistically significant improvement in event-free survival.
• ▪The phase 3 IMpower030 trial, sponsored by F. Hoffmann-La Roche, enrolled 397 patients in the stage IIB-IIIB wild-type population and 440 patients in the intent-to-treat wild-type population.
• ▪In the phase 3 IMpower030 trial, the median event-free survival in the stage IIB-IIIB wild-type non-small cell lung cancer population was 62.8 months with atezolizumab plus chemotherapy compared with 34.9 months with chemotherapy alone, which was not statistically significant.

Perioperative atezolizumab efficacy outcomes

• ▪Among patients in the phase 3 IMpower030 trial who achieved R0 resection, the median disease-free survival was 82.7 months with atezolizumab compared with 54.5 months with placebo.
• ▪In the intent-to-treat wild-type population of the phase 3 IMpower030 trial, the median event-free survival was 67.2 months with perioperative atezolizumab compared with 43.9 months with placebo.

Control group historical comparison

• ▪Study discussant Anne-Marie Dingemans suggested the strong outcomes in the phase 3 IMpower030 control group reflected the trial's selection of patients who had upfront confirmation of candidacy for curative R0 resection.
• ▪Compared with historical control populations, the phase 3 IMpower030 control group had a lower surgery cancellation rate of 11% versus 19% to 22%, and a longer median overall survival of 81.7 months versus 53.2 to 73.7 months.
• ▪Study investigator Benjamin Solomon stated that the placebo control group in the phase 3 IMpower030 trial performed better than historical controls from similar studies, which may explain why the primary endpoint did not reach statistical significance.