New Insights on Lenvatinib/Pembrolizumab Combo for Advanced Endometrial Cancer

Overview of Lenvatinib and Pembrolizumab in Endometrial Cancer

Recent discussions among medical professionals have brought to light the potential benefits of combining lenvatinib, a targeted drug, with pembrolizumab, an immunotherapy, for treating advanced endometrial cancer. This combination is especially relevant for patients whose tumors are proficient in mismatch repair (pMMR), which means their cancer cells are more stable and potentially harder to treat.

Case Study: A Closer Look

In one notable case, a 71-year-old postmenopausal woman with advanced endometrial cancer showed promising results after receiving lenvatinib and pembrolizumab as a second-line treatment. Initially treated with a combination of carboplatin and paclitaxel, she saw a marked improvement, but her cancer eventually returned, prompting the need for further intervention.

The patient’s initial treatments were well-tolerated, though she experienced some minor side effects like peripheral neuropathy and vomiting. After her cancer re-emerged, marked by elevated CA 125 levels and new metastases, she began the lenvatinib/pembrolizumab regimen.

Understanding Keynote-775/Study 309

The efficacy of the lenvatinib/pembrolizumab combination has been underscored by the KEYNOTE-775/Study 309 trial. This Phase 3 trial targeted patients with advanced, metastatic, or recurrent endometrial cancer who had previously undergone platinum-based chemotherapy. The study aimed to assess the combination’s impact on progression-free survival and overall survival rates.

Participants were grouped based on their mismatch repair status, among other factors. The trial compared patients receiving lenvatinib and pembrolizumab with those receiving doxorubicin or paclitaxel. The primary endpoint was to measure progression-free survival, while secondary endpoints included overall survival, overall response rate, and quality of life.

Clinical Outcomes and Findings

The trial revealed significant improvements in overall survival for patients receiving the lenvatinib/pembrolizumab combination. Specifically, in the pMMR subgroup, the median overall survival was 18 months, compared to 12 months for those treated with chemotherapy. These findings were statistically significant, with clear differentiation in survival curves between the two groups.

Additionally, the progression-free survival difference was notable. In the pMMR patients, those on the lenvatinib/pembrolizumab combination had a median progression-free survival of 7.3 months, compared to just 3.8 months for those on chemotherapy.

Response Rates and Duration

Overall response rates were also more favorable for the lenvatinib/pembrolizumab cohort. Approximately 30% of pMMR patients showed a response to the combination therapy, contrasted with a 15% response rate for those receiving chemotherapy. Furthermore, the duration of response was longer for those on the combination therapy, indicating a more sustained benefit.

Addressing Adverse Events

Despite the promising efficacy data, the combination therapy did present some notable adverse events. Patients frequently experienced hypertension, which was managed effectively but required regular monitoring. Other common side effects included hypothyroidism, diarrhea, and fatigue, generally managed with supportive care.

Interestingly, the onset of symptoms like hypertension occurred early in the treatment course, typically within the first two weeks, whereas hypothyroidism could present several months into therapy. This timeline underscores the importance of ongoing vigilance and patient management.

Current Recommendations

For patients with advanced endometrial cancer who are pMMR, the National Comprehensive Cancer Network (NCCN) guidelines now recommend exploring the lenvatinib and pembrolizumab combination as a viable second-line treatment option. This option comes after disease progression following initial systemic therapy.

As always, patient selection is crucial. Candidates for this combination therapy should have good performance status and no contraindications to the medications. Regular monitoring and management of side effects are essential to maximizing the therapy’s benefits while minimizing risks.

Conclusion

The combination of lenvatinib and pembrolizumab offers a promising option for patients with pMMR endometrial cancer, providing significant improvements in survival and disease control. Ongoing research and real-world patient experiences will continue to refine and optimize the use of this therapy in clinical practice.