The Phase 3 KEYLYNK-006 trial evaluating pembrolizumab with maintenance olaparib versus pembrolizumab with maintenance pemetrexed in first-line metastatic nonsquamous non-small-cell lung cancer (NSCLC) reached its primary completion on 2024-02-07. The study found that the pembrolizumab plus maintenance olaparib arm did not demonstrate superiority, with a median progression-free survival (PFS) of 7.1 Months compared to 8.3 Months for the pembrolizumab plus maintenance pemetrexed arm.

Background

Pembrolizumab (Keytruda) is an established immunotherapy used in various cancer types, including non-small-cell lung cancer. This study aimed to investigate whether adding the PARP inhibitor olaparib as maintenance therapy, following initial pembrolizumab-based treatment, could offer an advantage over the standard maintenance pemetrexed regimen in patients with metastatic nonsquamous NSCLC.

Trial design

The study, identified as NCT03976323, was a PHASE3 trial that enrolled 1003 participants with Carcinoma, Nonsquamous Non-small-cell Lung. The trial compared two maintenance treatment arms: pembrolizumab plus maintenance olaparib versus pembrolizumab plus maintenance pemetrexed. Initial treatment included pembrolizumab in combination with carboplatin or cisplatin. 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) per RECIST 1.1 by blinded independent clinical review (BICR).

Key results

For the primary endpoint of Progression-free Survival (PFS), the median PFS for the Pembrolizumab + Olaparib maintenance phase was 7.1 Months, while for the Pembrolizumab + Pemetrexed maintenance phase, it was 8.3 Months. The Hazard Ratio (HR) for PFS was 1.12 (95% Confidence Interval: 0.92 to 1.36), with a p-value of 0.8721, indicating no statistically significant difference.

Regarding Overall Survival (OS), the median OS for the Pembrolizumab + Olaparib arm was 20.7 Months, compared to 23.0 Months for the Pembrolizumab + Pemetrexed arm. The HR for OS was 1.04 (95% Confidence Interval: 0.87 to 1.25), with a p-value of 0.6649, also showing no statistically significant difference.

In terms of Quality of Life, the Least Squares Mean change from baseline in EORTC QLQ-C30 Global Health Status / Quality of Life score was -5.34 Scores on a scale for the Olaparib arm and -3.44 Scores on a scale for the Pemetrexed arm. The difference in LS Means was -1.9 (95% Confidence Interval: -5.16 to 1.36), with a p-value of 0.2533. The median Time to True Deterioration (TTD) in this score was 19.81 Months for Olaparib and 17.28 Months for Pemetrexed, with an HR of 0.97 (95% Confidence Interval: 0.76 to 1.24) and a p-value of 0.8125.

For the EORTC QLQ-LC13 Cough scale score, the Least Squares Mean change from baseline was -1.98 Scores on a scale for Olaparib and -1.82 Scores on a scale for Pemetrexed. The difference in LS Means was -0.16 (95% Confidence Interval: -4.02 to 3.71), with a p-value of 0.9364. Median TTD in cough score was not available for either arm, and the HR for TTD was 0.88 (95% Confidence Interval: 0.66 to 1.17) with a p-value of 0.3782.

What this means

The results of the KEYLYNK-006 trial indicate that the primary hypotheses were not met. Pembrolizumab plus maintenance olaparib did not demonstrate superiority in progression-free survival or overall survival compared to pembrolizumab plus maintenance pemetrexed in patients with first-line metastatic nonsquamous NSCLC. The numerical data for both PFS and OS showed slightly shorter median durations in the olaparib arm, and the hazard ratios with corresponding p-values confirm a lack of statistically significant benefit for the olaparib regimen over pemetrexed. Quality of life measures also did not show a significant advantage for the olaparib combination.

Source

These trial results were posted on ClinicalTrials.gov on 2024-02-07. The full details of the study, NCT03976323, are available on clinicaltrials.gov.