The Phase 3 KEYLYNK-006 Study of Pembrolizumab Plus Olaparib Versus Pembrolizumab Plus Pemetrexed as Maintenance Therapy for Metastatic Nonsquamous NSCLC.

INTRODUCTION

Poly (adenosine diphosphate-ribose) inhibitors, including olaparib, upregulate programmed cell death ligand 1, which may increase the efficacy of anti-programmed cell death protein 1 and anti-programmed cell death ligand 1 therapies.

METHODS

In the phase 3 KEYLYNK-006 trial (NCT03976323), eligible adults with previously untreated metastatic nonsquamous NSCLC without targetable genetic alterations who had complete response, partial response, or stable disease after induction therapy with four cycles of pembrolizumab 200 mg every three weeks, pemetrexed 500 mg/m, and carboplatin area under the concentration-time curve 5 mg/mL/min or cisplatin 75 mg/m were randomized in a one-to-one ratio to olaparib 300 mg orally twice daily or pemetrexed every three weeks, both given with up to 31 cycles of pembrolizumab every three weeks. Dual primary endpoints were progression-free survival (PFS) and overall survival (OS). Progression-free survival was tested at interim analysis 2 (i.e., final PFS analysis) and OS at final analysis (FA).

RESULTS

Of 1003 patients who received induction therapy, 672 (67.0%) were randomized to pembrolizumab plus olaparib (n = 337) or pembrolizumab plus pemetrexed (n = 335) in the intention-to-treat population. Median follow-up at FA was 39.9 (range: 28.1-51.5) months. At interim analysis 2, the median (95% confidence interval [CI]) PFS was 7.1 (5.6-8.7) months versus 8.3 (6.9-11.5) months in the olaparib versus pemetrexed groups (hazard ratio = 1.12, 95% CI: 0.92-1.36, p = 0.87). At FA, the median (95% CI) OS was 20.7 (18.0-24.8) months versus 23.0 (19.0-26.4) months (hazard ratio = 1.04, 95% CI: 0.87-1.25, p = 0.6649). Grade 3 to 5 maintenance treatment-related adverse events occurred in 26.1% versus 30.1% of patients, respectively.

CONCLUSION

Pembrolizumab plus maintenance olaparib did not improve PFS or OS versus pembrolizumab plus pemetrexed in previously untreated metastatic nonsquamous NSCLC without targetable genetic alterations.