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The Impact of Pembrolizumab and Olaparib Combination on Triple-Negative Breast Cancer Outcomes: A Closer Look at the KEYLYNK-009 Trial

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Zara Nwosu
New Update
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The Impact of Pembrolizumab and Olaparib Combination on Triple-Negative Breast Cancer Outcomes: A Closer Look at the KEYLYNK-009 Trial

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Recent research presented at the San Antonio Breast Cancer Symposium demonstrated that the combination of pembrolizumab and olaparib did not significantly improve outcomes for patients with locally recurrent inoperable or metastatic triple-negative breast cancer. However, a silver lining appeared for patients with BRCA mutations, who demonstrated improved progression-free survival (PFS) and overall survival (OS) with this treatment, hinting at a potential maintenance strategy for this subgroup.

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Details of the KEYLYNK-009 Trial

The KEYLYNK-009 trial, which included 271 patients, examined the effects of adding olaparib to pembrolizumab. The results showed no significant improvement in PFS or OS compared to pembrolizumab plus chemotherapy in the intention-to-treat population. While a numerical PFS improvement was observed among patients with BRCA mutations, it did not reach statistical significance among those with a PD-L1 combined positive score (CPS) ≥10. However, treatment-related adverse events were lower in the pembrolizumab-olaparib group compared to the pembrolizumab-chemotherapy group.

Additional Findings and Insights

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According to a report on Onclive.com, the combination of pembrolizumab (also known as Keytruda) and olaparib (also known as Lynparza) did not improve progression-free or overall survival compared to pembrolizumab plus chemotherapy in patients with locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC) who had previously received induction pembrolizumab plus chemotherapy. The median estimated OS in the intention-to-treat (ITT) population with pembrolizumab-olaparib was 25.1 months, with a median follow-up of 17.2 months in both the pembrolizumab-olaparib and pembrolizumab-chemotherapy arms.

Several newly registered targeted agents, including pembrolizumab, olaparib, talazoparib, sacituzumab govitecan, and trastuzumab deruxtecan, have shown promise in the treatment of patients with TNBC. In particular, adjuvant olaparib was found to prolong invasive disease-free survival and overall survival of patients with germline BRCA1/2 mutations. In PD-L1-positive patients, the addition of pembrolizumab to first-line chemotherapy increased the response rate and prolonged survival.

Conclusion

While the combination of pembrolizumab and olaparib did not significantly improve outcomes for patients with locally recurrent inoperable or metastatic triple-negative breast cancer in the KEYLYNK-009 trial, it did show potential as a maintenance strategy for patients with BRCA mutations. The lower incidence of treatment-related adverse events in the pembrolizumab-olaparib group compared to the pembrolizumab-chemotherapy group is also a promising finding. Further research is needed to fully understand the potential benefits and limitations of this treatment combination.

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