Krishnansu Tewari, MD
The invited discussant Krishnansu Tewari, MD, Professor in the Division of Gynecologic Oncology at the University of California, Irvine, called innovaTV 301 a “practice-changing study” that should result in full approval of tisotumab vedotin-tftv in the United States “and, importantly, will introduce a new cervical cancer medicine to Europe.”
As Dr. Tewari noted, advanced cervical cancer that recurs after first-line therapy is a high-risk scenario with an unmet treatment need. The first study to address this issue in patients who did not receive prior immunotherapy during first- or second-line chemotherapy, was the phase III EMPOWER trial, which found a median overall survival of 12.0 months with the anti–PD-1 agent cemiplimab-rwlc vs 8.5 months with chemotherapy (hazard ratio [HR] = 0.69).1 The current innovaTV 301 trial produced similar results for tisotumab vedotin, with a median overall survival of 11.5 months vs 9.5 months with chemotherapy (HR = 0.70). The response rate of 17.8% was also similar to the 16.4% response rate seen with cemiplimab, though it is lower than that shown in two other studies of tisotumab vedotin,2,3 Dr. Tewari pointed out.
Given the similar response rates with tisotumab vedotin and cemiplimab, the question, he said, is how to choose among the two treatments (assuming they are available) for second-line therapy in patients naive to checkpoint inhibitors. There is also the question of where best to use tisotumab vedotin: as monotherapy in the second line or as first-line therapy in combination with pembrolizumab, carboplatin, or bevacizumab (based on innovaTV 205).3
Currently, Dr. Tewari considers the following options to represent the evolving second-line landscape for second-line treatment of advanced cervical cancer: tisotumab vedotin monotherapy (approved in the United States but not in Europe); pembrolizumab monotherapy for patients with PD-L1–positive disease who are naive to checkpoint inhibitors; cemiplimab monotherapy in patients naive to checkpoint inhibitors (approved in Europe but not in the United States); and tisotumab vedotin plus pembrolizumab in patients naive to checkpoint inhibitors with PD-L1–positive disease (combined positive score1). Given that tissue factor does not seem to track with response or survival, the identification of clinical and/or molecular biomarkers is of great interest, he added.
DISCLOSURE: Dr. Tewari reported financial relationships with Merck, Eisai, GSK, Genentech/Roche, AstraZeneca, Seagen/Genmab, Regeneron, Morphotek, AbbVie, Karyopharm, and Immunogen.
REFERENCES
1. Tewari KS, Monk BJ, Vergote I, et al: Survival with cemiplimab in recurrent cervical cancer. N Engl J Med 386:544-555, 2022.
2. Coleman RL, Lorusso D, Gennigens C, et al: Efficacy and safety of tisotumab vedotin in previously treated recurrent or metastatic cervical cancer (innovaTV 204/GOG-3023/ENGOT-cx6): A multicentre, open-label, single-arm, phase 2 study. Lancet Oncol 22:609-619, 2021.
