In a groundbreaking move, the FDA has approved two new immunotherapy-chemotherapy options for patients with primary advanced or recurrent endometrial cancer. One of the options is the PD-1-directed immune checkpoint inhibitor pembrolizumab, also known as Keytruda, which is now approved in combination with carboplatin and paclitaxel for patients with either mismatch repair (MMR)-deficient or MMR-proficient disease, based on the results of the KEYNOTE-868/NRG-GY018 trial.
The randomized KEYNOTE-868/NRG-GY018 trial had two separate cohorts, including 222 patients with MMR-deficient tumors and 588 with MMR-proficient tumors. All patients were randomized to standard chemotherapy plus either pembrolizumab or placebo. The results showed significant improvement in progression-free survival (PFS) with the addition of pembrolizumab. In the MMR-deficient cohort, the median PFS was not reached in the pembrolizumab arm, as compared to 6.5 months for the group assigned to placebo, indicating a remarkable improvement in outcomes.
Durvalumab Approval
The second option approved by the FDA is the PD-L1 inhibitor durvalumab, also known as Imfinzi, in combination with the same chemotherapy regimen for women with MMR-deficient disease only, based on the results of the DUO-E trial. These results also demonstrated improvement in PFS with the addition of immunotherapy, particularly in the MMR-deficient group, which showed the most benefit from the treatment.
The DUO-E trial tested two investigational combinations added to standard carboplatin-paclitaxel chemotherapy. Regardless of MMR status, the addition of durvalumab to carboplatin-paclitaxel, followed by durvalumab maintenance, improved PFS versus chemotherapy plus placebo. In the 95 patients with MMR-deficient tumors, the median PFS was not reached in the durvalumab arm, indicating a significant advancement in patient outcomes.
Overall Impact and Future Outlook
These approvals mark a significant advancement in the treatment options available for patients with primary advanced or recurrent endometrial cancer. With the incidence and mortality of endometrial cancer expected to increase significantly in the coming decades, it is crucial to bring new and effective treatment options to patients at the earliest possible moment in their care.
Both pembrolizumab and durvalumab have shown promising results in improving PFS in patients with endometrial cancer, especially those with MMR-deficient tumors. The addition of immunotherapy to standard chemotherapy regimens has the potential to revolutionize the treatment landscape for this patient population.
The FDA’s approval of pembrolizumab and durvalumab as immunotherapy-chemotherapy options for endometrial cancer represents a major milestone in the fight against this disease. These advancements offer hope for improved outcomes and quality of life for patients facing this challenging diagnosis. The ongoing research and development in the field of immunotherapy continue to show promise in transforming cancer care and bringing new hope to patients and their families.
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