Avelumab Shows Potential Treating Patients With Rare Gestational Trophoblastic Tumors

Treatment with avelumab (Bavencio) potentially cured 8 of 15 women in a trial with gestational trophoblastic tumors resistant to single-agent chemotherapy.

A small, phase 2 study showed treatment with avelumab (Bavencio) potentially curing 8 of 15 women with gestational trophoblastic tumors (GTT) resistant to single-agent chemotherapy.

GTT is a very rare cancer that develops inside a woman’s uterus during or after pregnancy. This trial is the first exploring use of immunotherapy in patients with GTT, abnormal growths in the uterus that develop from placenta produced during conception.

Presented in a virtual scientific program of the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting, the trial results suggest that avelumab, a checkpoint inhibitor that blocks a protein—programmed-death ligand 1 (PD-L1)—on cancer cells that helps them hide from the body’s immune system, may be a new therapeutic option for GTT, which overexpresses PD-L1. In the study, cancer did not relapse in 8 patients at 29 months follow-up, and patients’ human chorionic gonadotropic (hCG) levels returned to normal.

"This proof-of-concept study shows that treatment with the immunotherapy avelumab works against these tumors when resistance to single-agent chemotherapy develops,” said lead author Benoit You, MD, PhD, medical oncologist at Centre Hospitalier Lyon-Sud and Lyon Investigational Center for Treatments in Oncology and Hematology in France, in a prepared statement. “Although more evidence is needed before changing clinical practice, these are highly promising results, suggesting that avelumab could prevent patients with chemo-resistant disease from the severe toxicity of chemotherapy combinations.”

Standard treatments of GTT rely on chemotherapy, as a single agent or polychemotherapy.

“If chemotherapy is associated with a high cure rate, it is also associated with significant toxicity,” You said during the presentation.

The majority of trophoblastic tumors relapse within 6 months, if not within the 12 months after treatment discontinuation. If disease has not relapsed after 12 months and monitoring of human chorionic gonadotropin (hCG) has concluded, researchers consider the patient cured, The hormone hCG is used as biomarker for GTT. The 15 patients in the study were a median age of 34 years with GTT that was resistant to mono-chemotherapy; 47% were stage III with metastases.

In this study, 7 patients achieved normal levels of hCG during treatment with avelumab and 1 had normalization after discontinuation of avelumab. Disease in these patients has not relapsed after 29 months follow-up, and normal levels of hCG has been maintained.

One patient who was successfully treated with avelumab later went on to have a healthy pregnancy. It was the first report of a normal pregnancy after a curative treatment with an immunotherapy agent, according to the researchers.

Avelumab resistance was observed in the remaining 7 patients, requiring chemotherapy with actinomycin-D or polychemotherapy with/without surgery.

Adverse effects (AEs) were generally mild, with 93% of patients having grade 1-2 drug-related AEs. Fatigue was the most common (33% of patients), followed by nausea and vomiting (33%), and infusion-related reactions (27%).

“Given the number of patients with disease that did not relapse, and reduced toxicity compared with standard single-agent chemotherapy, avelumab merits additional investigation,” said ASCO President Howard A. Burris III, MD, FACP, FASCO, in a prepared statement.

Researchers are conducting a similar trial for avelumab in the first-line setting. According to You, drug tolerance was better with avelumab than with chemotherapy.

REFERENCE

Immunotherapy Avelumab Shows Potential in Rare Gynecologic Cancer Resistant to Chemotherapy [news release]. Alexandria, VA; May 28, 2020: ASCO website. https://www.asco.org/about-asco/press-center/news-releases/immunotherapy-avelumab-shows-potential-rare-gynecologic-cancer Accessed June 1, 2020.