Immunotherapy Combos May Change Prognosis of Late-state or Recurrent EC

A pair of researchers is examining the pipeline for endometrial cancer (EC), outlining the phase 3 trials assessing novel approaches for the treatment of EC, the only gynecologic cancer with an increasing incidence and mortality.

Ramez N. Eskander and Matthew A. Powell focused on immunotherapy combinations, which they say may hold promise in the treatment of EC, particularly in late-stage or recurrent disease, which has limited treatment options.

“While identification of effective treatment strategies in the EC arena has been historically difficult, tremendous gains have been realized with the incorporation of immune checkpoint inhibitors,” the pair wrote. “To date, the greatest efficacy has been seen in the [mis- match-repair-deficient] or [microsatellite instability-high] populations, with the combination regimen of lenvatinib and pembrolizumab showing synergistic effects in [mismatch-repair-proficient] cohorts.”

One approach being taken is combining immune checkpoint inhibitors with chemotherapy in order to try and boost the rate of patients responding to treatment. The researchers note that as of yet, data on the approach is limited to preclinical data.

However, there are currently 4 prospective, phase 3 trials assessing how the addition of an immune checkpoint inhibitor to carboplatin and paclitaxel in patients with advanced and recurrent EC:

• In NRG GY018, pembrolizumab was added to the chemotherapy regimen as front-line, adjuvant therapy for patients with pMMR and dMMR, or in patients who completed adjuvant therapy at least a year prior to study entry
• The randomized RUBY trial of patients with advanced stage or recurrent EC is assessing the addition of dostarlimab to the chemotherapy combination
• In the AtTEnd trial of patients with advanced stage or recurrent EC and measurable disease, atezolizumab was assed to the chemotherapy regimen
• The 3-arm DUO-E trial will determine the effect of adding olaparib to immunotherapy in the maintenance setting

Another approach being taken is adding antiangiogenic therapy with immunotherapy, which the researchers say has shown great promise. A current phase 3 study, the ENGOT-EN9/LEAp-001 study is a randomized, open-label trial comparing combination therapy with pembrolizumab and lenvatinib to treatment with carboplatin and paclitaxel in patients with newly diagnosed advanced stage or recurrent EC.

“We eagerly await the results of the discussed phase III clinical trials to determine whether alternate drug combinations hold promise,” wrote the researchers. “It will also be important to explore drug sequencing as additional treatment options become available. Certainly, the magnitude of benefit with the various combinations will inform treatment decisions as we attempt to weigh oncologic gains against treatment-related side effects.”

Reference

Eskander R, Powell M. Immunotherapy as a treatment strategy in advanced stage and recurrent endometrial cancer: review of current phase III immunotherapy clinical trials. Ther Adv Med Oncol. 2021;13:1-9.