KEY TAKEAWAYS
- The KEYLYNK-009 phase II trial aimed to assess whether pembro + olaparib surpasses pembro + chemo for survival and safety in platinum-sensitive TNBC patients with first-line pembrolizumab + chemo-induced clinical benefit.
- The primary endpoints were PFS per RECIST v1.1 by BICR and OS.
- Pembro + olaparib showed promise as a maintenance strategy for tBRCAm-positive advanced TNBC with no new safety concerns and possibly fewer side effects than pembro + chemo but requires further validation.
Pembrolizumab (pembro) + chemotherapy (chemo) demonstrated significant progression-free survival (PFS) and overall survival (OS) improvements in untreated PD-L1-positive locally recurrent or metastatic triple-negative breast cancer (TNBC) in the KEYNOTE-355 study. Seeking tolerable maintenance regimens, the PARP inhibitor olaparib, known for efficacy in platinum-sensitive tumors, holds promise when combined with PD-1/PD-L1 inhibitors.
Hope Rugo and her team conducted the study that aimed to compare the efficacy and safety of pembro + olaparib vs pembro + chemo as maintenance therapy in TNBC patients with prior clinical benefit from pembro + platinum-based chemotherapy.
Patients with untreated, measurable TNBC received up to 6 cycles of pembro 200 mg + chemo(carboplatin AUC 2 + gemcitabine 1000 mg/m2 on days 1 and 8) every 3 wk (Q3W). Those with complete response (CR), partial response (PR), or SD after 4-6 cycles were randomized 1:1 to pembro + olaparib or pembro + continued chemo. Olaparib or chemo was continued until progression or unacceptable toxicity, and pembro for up to 35 cycles(including induction treatment). Stratification included induction response(CR or PR vs SD, by RECIST v1.1), tumor PD-L1 status(CPS ≥1 vs CPS < 1), and tumor genomic status (tBRCAm vs tBRCAwt).
The dual primary endpoints were PFS and OS from randomization in all patients; secondary endpoints included PFS and OS in specific subgroups and safety assessment.
Among 460 patients receiving induction therapy, 271 were randomized to pembro + olaparib (n=135) or pembro + chemo (n=136). As of the Dec 15, 2022 cutoff (median follow-up 17.2 mo), maintenance pembro + olaparib did not significantly improve PFS or OS compared to pembro + chemo after induction. Longer median PFS with pembro + olaparib was noted in tBRCAm patients but not in those with PD-L1 CPS ≥10 tumors; a similar trend was observed for OS.
In 268 treated patients, treatment-related adverse events(TRAEs) were found in 114 of 135 patients with pembro+olaparib (84.4%). For pembro+chemo the reported TRAEs were in 128 of 133 pts(96.2%), pembro + olaparib had lower grade ≥3 TRAEs (32.6%) than pembro + chemo (68.4%), with fewer discontinuations (8.9% vs 19.5%) for TRAEs.
The reported outcomes showed that the overall advanced TNBC population did not meet primary PFS and OS endpoints. Promising trends favoring PFS and OS improvements were evident in tBRCAm patients treated with pembrolizumab + olaparib compared to pembrolizumab + chemotherapy, suggesting a potential maintenance strategy.
Further data are needed for confirmation. Notably, no new safety signals were observed, and the pembrolizumab + olaparib group exhibited fewer TRAEs than the pembro + chemo group. The study was sponsored by Merck Sharp & Dohme LLC.
Source: https://atgproductions.net/atgclients/sabcs/2023_SABCS_Abstract_Report-12-1-23_Compressed.pdf
Clinical Trial: https://clinicaltrials.gov/study/NCT04191135
Rugo H, Robson M, Im S, et al.’’ Pembrolizumab + Olaparib vs Pembrolizumab + Chemotherapy After Induction With Pembrolizumab + Chemotherapy for Locally Recurrent Inoperable or Metastatic TNBC: Randomized Open-Label Phase 2 KEYLYNK-009 Study.’’ Presented at: SABCS 2023 (GS01-05).
