Recently, the FDA has approved two new immunotherapy-chemotherapy options for patients with primary advanced or recurrent endometrial cancer. This announcement marks a significant advancement in the treatment options available for patients with this type of cancer. The approval of these treatments comes as a result of successful phase III trials that demonstrated improved progression-free survival (PFS) with the addition of immunotherapy to standard chemotherapy regimens.
Pembrolizumab Approval and Trial Results
One of the approved treatments is the PD-1-directed immune checkpoint inhibitor pembrolizumab, in combination with carboplatin and paclitaxel. This treatment is approved for patients with either mismatch repair (MMR)-deficient or MMR-proficient disease. The results of the KEYNOTE-868/NRG-GY018 trial showed promising outcomes for patients in both cohorts. In the MMR-deficient cohort, the addition of pembrolizumab resulted in a median PFS that was not reached, compared to 6.5 months with placebo. Similarly, in the MMR-proficient cohort, the addition of pembrolizumab extended median PFS to 11.1 months compared to 8.5 months with chemotherapy alone. Overall survival (OS) data showed a trend favoring the pembrolizumab arms in both cohorts.
The other approved treatment is the PD-L1 inhibitor durvalumab, in combination with the same chemotherapy regimen. This treatment is approved for women with MMR-deficient disease only. The DUO-E trial showed that the addition of durvalumab to carboplatin-paclitaxel chemotherapy improved PFS versus chemotherapy plus placebo. Patients with MMR-deficient tumors saw the most benefit from the addition of durvalumab, with a median PFS that was not reached in the durvalumab arm compared to 7 months in the placebo arm.
Importance of New Treatment Options
With the incidence and mortality of endometrial cancer expected to increase significantly in the coming decades, the approval of these new treatment options is crucial. The addition of immunotherapy to standard chemotherapy regimens has shown to provide important clinical benefits for patients with endometrial cancer. The results of these trials offer hope for improved outcomes and better survival rates for patients with this disease.
Both pembrolizumab and durvalumab showed increased adverse events (AEs) when added to standard chemotherapy. These AEs were consistent with the known safety profiles of these immunotherapy agents, as well as carboplatin and paclitaxel. However, there was a higher incidence of rash noted with the addition of pembrolizumab. Common AEs with durvalumab included peripheral neuropathy, musculoskeletal pain, nausea, alopecia, fatigue, among others. Serious AEs were reported in 30% of patients, with rash and constipation being the most common.
The FDA’s approval of pembrolizumab and durvalumab in combination with chemotherapy regimens represents a significant step forward in the treatment of endometrial cancer. These new immunotherapy options offer hope for improved outcomes and survival rates for patients with this disease. The results of these trials highlight the importance of bringing new treatment options to patients at the earliest possible moment in their care. With the continued increase in the incidence and mortality of endometrial cancer, it is essential to continue to explore and develop new and effective treatment options for patients.
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