A Case Series: Activity of Pembro-Lenvatinib in dMMR EC Who Have Not Responded to Pembro-Mono

Summary for Physicians: Interpretation of Findings From Key Studies and Case Reports in Advanced EC

Dr Birrer to Dr Naumann: Activity of Pembrolizumab and Lenvatinib in dMMR EC Patients Who Did Not Respond to Pembrolizumab Monotherapy: A Case Series (P. Rose et al., Gynecol Oncol Rep, 2023)

• Study Overview:
  • Dr Naumann would begin by discussing the case series by P. Rose et al. (2023), which focuses on patients with dMMR cancer who did not respond to pembrolizumab monotherapy. This study investigates the potential of combining pembrolizumab with lenvatinib as a second-line therapy in these patients who developed resistance to pembrolizumab alone.
    
• Efficacy of Pembrolizumab and Lenvatinib Combination:
  • Dr Naumann would likely emphasize that this study shows promising results for the combination of pembrolizumab and lenvatinib, especially in patients with dMMR who did not respond to pembrolizumab monotherapy. The addition of lenvatinib, an antiangiogenic agent, to pembrolizumab, a PD-1 inhibitor, may overcome the resistance that can develop after a single-agent immune checkpoint inhibitor therapy.
  • The combination therapy works by targeting both the immune microenvironment (via pembrolizumab) and the tumor vasculature (via lenvatinib), potentially providing a synergistic effect that leads to better treatment outcomes, even in patients with IO-resistant disease.
    
• Clinical Implications:
  • Dr Naumann would highlight how this study provides an important insight into second-line treatment options for advanced EC. Specifically, it suggests that pembrolizumab and lenvatinib could be a viable treatment option for patients who did not respond to pembrolizumab monotherapy, particularly for those with dMMR/microsatellite instability (MSI)-high tumors, which are more likely to respond to immune therapies.
  • He may also point out that biomarker-driven treatment decisions are crucial in identifying patients who will benefit most from this combination. This is especially relevant for dMMR patients, who have shown a better prognosis with immune checkpoint inhibitors and may respond better to this combination treatment.
    
• Safety and Toxicity:
  • Dr Naumann would likely discuss the safety profile of the pembrolizumab-lenvatinib combination, noting that while it offers substantial benefits, it also comes with risks. Both pembrolizumab and lenvatinib have known adverse effects, such as immune-related toxicities (eg, colitis and hepatitis) and hypertension or fatigue from lenvatinib.
  • Clinicians need to closely monitor patients for adverse effects and adjust treatment protocols as necessary to manage these potential toxicities, ensuring the patient’s overall well-being while optimizing therapeutic outcomes.
    
• Future Directions:
  • Dr Naumann would conclude by discussing the need for further clinical trials to validate the combination of pembrolizumab and lenvatinib as a second-line therapy in advanced EC. Larger, randomized trials could better define the ideal patient population and optimal dosing schedules.
  • The study opens the door to further exploration of combination therapies and personalized treatment approaches based on tumor biology and prior treatment history.
    

Summary:

Dr Naumann interprets the findings of P. Rose et al. (2023), emphasizing that the pembrolizumab-lenvatinib combination shows promising efficacy for patients with dMMR EC who did not respond to pembrolizumab monotherapy. The combination may overcome resistance and provide a beneficial second-line treatment option for these patients. He also underscores the importance of biomarker-driven treatment and the need for close monitoring for adverse events associated with this combination. Finally, he highlights the need for further studies to refine this approach and better understand how to optimize patient selection and treatment regimens.