EVOKE-03 Trial: Sacituzumab Fails to Boost Survival

Adding the antibody-drug conjugate sacituzumab govitecan to pembrolizumab immunotherapy did not significantly improve survival for patients with untreated metastatic non-small cell lung cancer. These results from the phase III EVOKE-03 trial were presented by Dr. Giannis Mountzios of Henry Dunant Hospital Center in Athens at the World Conference on Lung Cancer in Seoul.

Median progression-free survival was 11.8 months for patients receiving the combination of sacituzumab govitecan (sold as Trodelvy) and pembrolizumab (Keytruda). For those receiving pembrolizumab alone, it was 7.7 months. This 4.1-month difference, however, did not meet the trial's prespecified statistical threshold for significance. An interim analysis of overall survival, a dual primary endpoint, showed a slight numerical advantage for the control arm at 22.8 months versus 21.5 months for the combination.

Safety and Efficacy Findings

Treatment-emergent adverse events occurred more often in the group receiving the antibody-drug conjugate. This included serious events, those leading to treatment discontinuation, and fatal events. Dr. Mountzios stated the safety profile was consistent with the known profiles of each drug, with no new toxicities observed.

The confirmed objective response rate was 55.6% for the combination therapy, compared to 43.7% for monotherapy. The disease control rate was also numerically higher at 83.3% versus 73.1%. The median duration of response was nearly identical between the two groups, at approximately 21.3 to 21.4 months.

Expert Analysis and Trial Context

Discussing the findings at the conference, Dr. Ji-Youn Han of South Korea's National Cancer Center noted a familiar pattern of attrition from phase II to phase III results. She pointed out that pembrolizumab monotherapy set a high bar with a 44.8% response rate in the earlier KEYNOTE-024 trial. While the phase II EVOKE-02 study of the sacituzumab combination showed a 66.7% response rate, it involved only 30 patients. The drop to 55.6% in the larger EVOKE-03 trial suggested the added drug acts like chemotherapy, turning non-responders into short-term responders without creating a long survival tail.

"Pembrolizumab monotherapy remains a standard for PD-L1-high groups," said Dr. Han. "Sacituzumab govitecan plus pembrolizumab should not be pursued in this setting outside of clinical trials."

Trial Design and Patient Population

The EVOKE-03 trial enrolled 620 patients internationally. All had untreated stage IV non-small cell lung cancer with a PD-L1 tumor proportion score of 50% or higher, and no actionable EGFR, ALK, or ROS1 mutations. Patients with untreated or unstable brain metastases were excluded. The dual primary endpoints were progression-free survival and overall survival, with secondary endpoints including objective response rate and safety.

The primary analysis was conducted after a median follow-up of 14.7 months. The hazard ratio for progression-free survival favoring the combination was 0.81, with a P-value of 0.0250. The trial protocol, however, required a P-value of 0.007 for statistical significance.

Prespecified subgroup analyses suggested a progression-free survival benefit for the combination in certain populations, including patients younger than 65 and those from East Asia. Prespecified analyses for patients from East Asia and China also suggested an overall survival benefit for the sacituzumab arm, but these differences did not achieve statistical significance. Dr. Han concluded that future trials need overall survival as a primary endpoint with better biomarker selection.