Trial results for the KEYLYNK-006 study (NCT03976323) comparing pembrolizumab plus maintenance olaparib versus pembrolizumab plus maintenance pemetrexed in first-line metastatic nonsquamous non-small-cell lung cancer were posted on ClinicalTrials.gov on 2025-02-06. The study found that the olaparib combination did not demonstrate superiority for progression-free survival or overall survival compared to the pemetrexed combination, with median progression-free survival of 7.1 months versus 8.3 months, respectively.
Background
Metastatic nonsquamous non-small-cell lung cancer (NSCLC) is a challenging condition, and first-line treatment strategies often involve immunotherapy combinations. This study investigated two maintenance therapy approaches following initial treatment with pembrolizumab and chemotherapy (carboplatin or cisplatin) to determine if adding olaparib offered an advantage over pemetrexed.
Trial design
The completed Phase 3 KEYLYNK-006 trial (NCT03976323) enrolled 1003 participants with Carcinoma, Nonsquamous Non-small-cell Lung. The study aimed to compare pembrolizumab plus maintenance olaparib against pembrolizumab plus maintenance pemetrexed. The primary hypotheses were that pembrolizumab plus maintenance olaparib would be superior to pembrolizumab plus maintenance pemetrexed with respect to progression-free survival (PFS) and overall survival (OS).
Key results
Key efficacy and quality of life outcomes were reported:
- Progression-free Survival (PFS): The median PFS was 7.1 months for the Pembrolizumab + Olaparib group and 8.3 months for the Pembrolizumab + Pemetrexed group. The Hazard Ratio was 1.12 (95% Confidence Interval: 0.92, 1.36), with a p-value of 0.8721.
- Overall Survival (OS): The median OS was 20.7 months for the Pembrolizumab + Olaparib group and 23.0 months for the Pembrolizumab + Pemetrexed group. The Hazard Ratio was 1.04 (95% Confidence Interval: 0.87, 1.25), with a p-value of 0.6649.
- Change from Baseline in EORTC QLQ-C30 Global Health Status / Quality of Life Scale Score: The least squares mean change was -5.34 for the Pembrolizumab + Olaparib group and -3.44 for the Pembrolizumab + Pemetrexed group. The difference in least squares means was -1.9 (95% Confidence Interval: -5.16, 1.36), with a p-value of 0.2533.
- Time to True Deterioration (TTD) in EORTC QLQ-C30 Global Health Status / Quality of Life Scale Score: The median TTD was 19.81 months for the Pembrolizumab + Olaparib group and 17.28 months for the Pembrolizumab + Pemetrexed group. The Hazard Ratio was 0.97 (95% Confidence Interval: 0.76, 1.24), with a p-value of 0.8125.
- Change from Baseline in EORTC QLQ-LC13 Cough Scale Score: The least squares mean change was -1.98 for the Pembrolizumab + Olaparib group and -1.82 for the Pembrolizumab + Pemetrexed group. The difference in least squares means was -0.16 (95% Confidence Interval: -4.02, 3.71), with a p-value of 0.9364.
- TTD in EORTC QLQ-LC13 Cough Scale Score: The median TTD was NA for the Pembrolizumab + Olaparib group and NA for the Pembrolizumab + Pemetrexed group. The Hazard Ratio was 0.88 (95% Confidence Interval: 0.66, 1.17), with a p-value of 0.3782.
What this means
The results from the KEYLYNK-006 trial indicate that pembrolizumab plus maintenance olaparib did not demonstrate superiority over pembrolizumab plus maintenance pemetrexed for the primary endpoints of progression-free survival and overall survival in patients with first-line metastatic nonsquamous NSCLC. The numerical trends for PFS and OS favored the pemetrexed arm, and none of the comparisons for key efficacy or quality of life outcomes reached statistical significance, as evidenced by the high p-values and confidence intervals that crossed 1 for hazard ratios or included 0 for differences in means. This suggests that the addition of olaparib in this maintenance setting did not provide a clinical benefit over pemetrexed.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT03976323, titled "Study of Pembrolizumab With Maintenance Olaparib or Maintenance Pemetrexed in First-line (1L) Metastatic Nonsquamous Non-Small-Cell Lung Cancer (NSCLC) (MK-7339-006, KEYLYNK-006)," were posted on 2025-02-06 on clinicaltrials.gov.