Susana M. Campos, MD, MPH, clinical director of the Division of Gynecologic Oncology and director of Educational Initiatives at Dana-Farber Cancer Institute, and an assistant professor of medicine at Harvard Medical School, discussed how oncologists should approach immunotherapy rechallenge in gynecologic cancers. Unlike renal cell carcinoma, where a 1-year immune checkpoint inhibitor-free interval is often used to guide retreatment, no such consensus yet exists for gynecologic cancers.
As part of a Satellite Sessions post-program conversation, Campos reviewed mechanisms of immune resistance, including B2M and JAK1/2 mutations, and walked through retrospective data on adding lenvatinib (Lenvima) after progression on pembrolizumab (Keytruda) monotherapy in mismatch repair-deficient (dMMR) endometrial cancer.1,2
Transcript:
CancerNetwork: How critical is the duration of the IO-free interval when considering a rechallenge? Is a consensus emerging for gynecologic cancers, similar to the 1-year rule in renal cell carcinoma?
Campos: It’s a great question, and unfortunately, the evidence is lagging [behind] the need in clinical practice. We have no prospective trials to date that have guided our clinical practice. We’re still at the area where we’re trying to understand the mechanisms of immune resistance. We do know there are some genetic alterations, such as B2M and JAK1/2 mutations, that have been implicated in immune resistance. There are also other elements, like upregulation of VEGF, infiltration of regulatory T cells, or myeloid-derived suppressor cells. However, given this question, we’ve had to rely specifically on retrospective studies, and some of those have been a little bit illuminating. One of them is by [Peter] Rose, MD, and colleagues, who looked at 8 patients with dMMR endometrial cancer who had progressed on pembrolizumab. What he saw was a 75% response rate with the addition of lenvatinib. Now, was this related to a reversal of resistance, or did we simply introduce another active agent? We don’t know. There’s been another study by Morton and colleagues that reported as high as a 54.5% response [rate] in patients previously treated with IO. We don’t have that answer.
References
1. Rose PG, Feldman M, Podzielinski I, Petty AP, Vargas R. Activity of pembrolizumab and lenvatinib in mismatch repair deficient (dMMR) endometrial cancer patients who have failed pembrolizumab monotherapy: a case series. Gynecol Oncol Rep. 2023;50:101303. doi:10.1016/j.gore.2023.101303
2. Morton M, Marcu I, Levine M, et al. Evaluation of Efficacy and Adverse Events After Second Immunotherapy Exposure in Endometrial and Cervical Carcinoma. Obstet Gynecol. 2023;142(2):360-363. doi:10.1097/AOG.0000000000005243
