Recently, the FDA has approved two new immunotherapy-chemotherapy options for patients with primary advanced or recurrent endometrial cancer. One of these options is the PD-1-directed immune checkpoint inhibitor pembrolizumab, also known as Keytruda. This drug has been approved in combination with carboplatin and paclitaxel for patients with either mismatch repair (MMR)-deficient or MMR-proficient disease. The approval was based on the results of the KEYNOTE-868/NRG-GY018 trial. This clinical trial included two separate cohorts, with 222 patients having MMR-deficient tumors and 588 patients having MMR-proficient tumors. The results showed an 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, compared to 6.5 months in the placebo group, with a hazard ratio (HR) of 0.30 and a P-value of less than 0.0001. Meanwhile, in the MMR-proficient cohort, the addition of pembrolizumab led to a median PFS of 11.1 months, compared to 8.5 months with chemotherapy alone, with a HR of 0.60 and a P-value of less than 0.0001. Overall survival (OS) data were still immature at the time of the analysis, but preliminary results showed a trend favoring the immunotherapy arms in both cohorts. The incidence of adverse events (AEs) increased with the addition of pembrolizumab, with grade 3 or higher AEs occurring in 55-63% in the pembrolizumab group compared to 45-47% in the placebo group.
The second immunotherapy option approved by the FDA for endometrial cancer patients is the PD-L1 inhibitor durvalumab, also known as Imfinzi. This drug has been approved in combination with the same chemotherapy regimen of carboplatin and paclitaxel but specifically for women with MMR-deficient disease. The approval was based on the results of the DUO-E trial, which showed an improvement in PFS with the addition of durvalumab to the chemotherapy regimen. The trial included 95 patients with MMR-deficient tumors, and the results indicated a significant benefit in terms of PFS with durvalumab compared to placebo, with a HR of 0.42 and a P-value of less than 0.0001.
Common adverse events associated with durvalumab included peripheral neuropathy, musculoskeletal pain, nausea, alopecia, fatigue, abdominal pain, constipation, rash, diarrhea, vomiting, and cough. Serious AEs occurred in 30% of patients, with rash or constipation being the most common serious AEs at 4.5% each. Overall, AEs leading to the discontinuation of durvalumab occurred in 11% of patients. The approval of durvalumab highlights the clinical benefits it provides to patients with mismatch repair-deficient endometrial cancer, according to DUO-E investigator Shannon Westin, MD.
The recent approvals of pembrolizumab and durvalumab as immunotherapy-chemotherapy options for endometrial cancer patients represent significant advancements in the treatment landscape for this patient population. These approvals provide new treatment options for patients with primary advanced or recurrent endometrial cancer, particularly those with mismatch repair-deficient tumors. Further research and clinical trials are needed to fully understand the potential of these immunotherapy options and their long-term effects on patient outcomes.
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