Primary completion results for the Phase 3 KEYNOTE-671 trial (NCT03425643) evaluating pembrolizumab (Keytruda) in resectable non-small cell lung cancer (NSCLC) were posted on 2023-07-10. The study showed that pembrolizumab combined with neoadjuvant/adjuvant chemotherapy significantly improved event-free survival (EFS) to a median of 47.2 months compared to 18.3 months for placebo, representing a hazard ratio of 0.59.

Background

Pembrolizumab (Keytruda) is an established immunotherapy. This trial investigated its use in resectable non-small cell lung cancer (NSCLC), a common and serious form of lung cancer, in a neoadjuvant and adjuvant setting.

Trial design

The Phase 3 KEYNOTE-671 study (NCT03425643) enrolled 797 participants with resectable Stage II, IIIA, and resectable IIIB (T3-4N2) non-small cell lung cancer (NSCLC). The trial evaluated pembrolizumab in combination with platinum doublet neoadjuvant chemotherapy (cisplatin, gemcitabine, or pemetrexed) before surgery, followed by pembrolizumab alone after surgery. The comparator arm received platinum doublet neoadjuvant chemotherapy and placebo before surgery, followed by placebo alone after surgery. The primary hypothesis focused on improving event-free survival (EFS).

Key results

  • Median event-free survival (EFS) was 47.2 Months for participants receiving pembrolizumab with neoadjuvant/adjuvant chemotherapy, compared to 18.3 Months for those receiving placebo. This represented a hazard ratio of 0.59 (95% Confidence Interval: 0.48, 0.72; p-value: 1e-05).
  • For overall survival (OS), the median was NA for the pembrolizumab arm and 52.4 Months for the placebo arm, with a hazard ratio of 0.72 (95% Confidence Interval: 0.56, 0.93; p-value: 0.00517).
  • The major pathological response (mPR) rate was 30.2 Percentage of Participants in the pembrolizumab arm versus 11.0 Percentage of Participants in the placebo arm. The difference in percentage was 19.2% (95% Confidence Interval: 13.9, 24.7; p-value: 1e-05).
  • The pathological complete response (pCR) rate was 18.1 Percentage of Participants for pembrolizumab compared to 4.0 Percentage of Participants for placebo. The difference in percentage was 14.2% (95% Confidence Interval: 10.1, 18.7; p-value: 1e-05).
  • Changes from baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status scores during the neoadjuvant phase showed a least squares mean of -9.31 for pembrolizumab and -10.73 for placebo. The difference in least square means was 1.43 (95% Confidence Interval: -1.64, 4.49; p-value: 0.3611).
  • During the adjuvant phase, changes from baseline in EORTC QLQ-C30 Global Health Status scores were a least squares mean of -1.52 for pembrolizumab and -3.74 for placebo. The difference in least square means was 2.22 (95% Confidence Interval: -0.58, 5.02; p-value: 0.1197).

What this means

The significant improvement in event-free survival, major pathological response, and pathological complete response rates observed with pembrolizumab in combination with chemotherapy suggests a substantial clinical benefit for patients with resectable non-small cell lung cancer. While overall survival data for the pembrolizumab arm is not yet mature, the hazard ratio for OS also indicates a positive trend. These findings support the potential for pembrolizumab to become an important treatment option in the neoadjuvant/adjuvant setting for this patient population, aiming to reduce recurrence and improve long-term outcomes. Quality of life measures did not show a statistically significant difference between the two arms.

Source

This information was sourced from ClinicalTrials.gov, detailing the primary completion results posted on 2023-07-10 for study NCT03425643. The full details are available on clinicaltrials.gov.