Two gynecologic oncologists and ASCO’s Chief Medical Officer and Executive Vice President Richard L. Schilsky, MD, FACP, FSCT, FASCO, commented on the findings of the TROPHIMMUN trial for The ASCO Post.

“The authors demonstrate efficacy of a new treatment approach for gestational trophoblastic tumors in patients who have not responded to first-line chemotherapy,” said Karen McLean, MD, PhD, Assistant Professor of Gynecologic Oncology at Michigan Medicine, Ann Arbor. “The reported side effects are as expected for immunotherapy, and overall, the treatment is well tolerated. These side effects may be fewer than those observed in other clinical trials with immunotherapy due to the generally younger age of patients with gestational trophoblastic tumors, and in this patient population, the side effects of immunotherapy may be preferred over those of standard chemotherapy.”

Dr. McLean continued: “This treatment approach warrants further study in women with gestational trophoblastic tumors, including its potential use in the upfront setting. And head-to-head phase III trials against multiagent chemotherapy regiments are warranted in patients whose disease fails to respond to first-line chemotherapy to assess both response rates and patient-reported outcomes.” Dr. McLean hopes to see further investigation into potential biomarkers of response, “as the authors reported that response was not related to stage or FIGO score.”

Richard L. Schilsky, MD, FACP, FSCT, FASCO

Karen McLean, MD, PhD

Konstantin Zakashansky, MD

‘An Important Contribution’

Konstantin Zakashansky, MD, Director of Minimally Invasive Surgery at Mount Sinai Health System and Associate Professor of Gynecologic Oncology at Icahn School of Medicine at Mount Sinai, explained why targeting the interaction of PD-1/PD-L1 could be an effective therapeutic strategy for chemoresistant gestational trophoblastic tumors. “In preclinical models, loss of PD-L1 signaling results in fetal rejection. At the same time, multiple previous studies have found that gestational trophoblastic neoplasia strongly expresses PD-L1, thus suggesting the ligand is involved in tumor immune evasion,” he said.

Noting that several case reports have suggested pembrolizumab is effective in treating gestational trophoblastic neoplasia, Dr. Zakashansky said he was not surprised avelumab “would work similarly.” He considers TROPHIMMUN an important contribution to proving the worth of this strategy, although he acknowledged it is a small study with few details.

Moving Forward

“Gestational trophoblastic neoplasia is a highly curable disease, with primary remission rates after single-agent therapy varying from 49% to 93%, depending on the specific regimen used. Therefore, interpreting these new data requires detailed information on which primary therapy patients in this cohort received,” he noted.

Dr. Zakashansky further pointed out that for patients who require multiagent chemotherapy, cure rates are close to 100%. “In that context, the 53% remission rate seen in this nonrandomized study does not seem acceptable,” he offered. However, given avelumab’s “demonstrable monotherapeutic efficacy and favorable side-effect profile,” he would like to see how the drug can be incorporated into the management of gestational trophoblastic neoplasia. For this, he added, more information will be necessary to properly evaluate the approach and develop a viable strategy.

Words of Caution

Finally, Dr. Schilsky offered his take to The ASCO Post on the potential use of avelumab as initial treatment in this patient population. “Let’s remember, 70% of these women can be cured with methotrexate, which costs practically nothing, financially. So, one would question whether to substitute a highly effective, inexpensive therapy with immunotherapy—which, granted, might be more effective but remains unproven—and certainly will be more expensive. To give immunotherapy upfront to demonstrate efficacy in the very small proportion who won’t be cured otherwise…is a big leap in the wrong direction.” 

DISCLOSURE: Dr. McLean reported no conflicts of interest. Dr. Zakashansky has acted as an advisor or consultant for Verb Surgical. Dr. Schilsky has received institutional research funding from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Genentech/Roche, Lilly, Merck, and Pfizer and has been reimbursed for travel, accommodations, or other expenses by Varian.