ASCO 2020: Immunotherapy Gives Hope to Women with Placental Cancer

By Ruchi Jhonsa, Ph.D.

Localized in the placenta during pregnancy, gestational trophoblastic tumors (GTT) affects 1 in 10000 women. It affects the cells that produce human chorionic gonadotrophin hormone and causes a rise in the blood levels of the hormone. Currently, the standard of care for GTT relies on chemotherapy, which, although associated with a high cure rate, can be toxic to the patient. Additionally, most GTT patients develop chemotherapy resistance to a platinum-based regimen. This warrants the development of innovative therapies that are effective and safe. The evaluation of Merck and Pfizer’s avelumab (Bavencio) as an immunotherapeutic approach for GTT was discussed in the ASCO virtual meeting.

Bavencio as a Potential Treatment

Immunotherapy is based on the idea that cancer cells evade immune attack by engaging the negative signal receptor on the T cells that prevent the immune cell from attacking them. One such negative signal receptor-ligand pair is the PD-1/PD-L1 proteins. The PD-L1 checkpoint protein was observed to be constitutively expressed in all GTT subtypes indicating that PD-L1 blocker may be a potential treatment for this type of cancer. The PD-L1 blocker, avelumab, has been successful in the remission of varied cancer types. Its effectiveness as GTT treatment was evaluated in the TROPHIMMUN trial.

The TROPHIMMUN Trial

The academic Phase II trial sponsored by Lyon University Hospital (France) in collaboration with the network of the French Gestational Trophoblastic disease center evaluated the efficacy of avelumab in patients with chemoresistant GTT. The results from this trial presented by Dr. Benoit You, MD, Ph.D., demonstrated that avelumab is effective and safe for women. This is the first trial of PD-L1 targeting immunotherapy in GTT patients.

The trial enrolled a total of 17 patients in two years, of which only 15 were found treatable and assessable. The study recruited all the patients despite their PD-L1 status. When patients joined the trial, they had already undergone a round of chemotherapy with methotrexate or actinomycin-D. Patients were administered a 10mg/kg drug every two weeks until hCG normalization followed by three consolidation cycles. Surprisingly, none of the patients were evaluated. Treatment with avelumab was considered effective if the levels of hCG returned to normal.

Results showed that in eight women, hCG returned to normal levels after avelumab treatment. Interestingly, the drug did not affect fertility, and one patient got pregnant after one year of termination of the treatment. All eight patients did not show any sign of relapse in 27 months follow up time after treatment discontinuation. However, the remaining seven patients had to quit because of the ineffectiveness of avelumab in reducing cancer growth and showed hCG normalization with surgery or actinomycin treatment. The safety profile of the drug is also impressive. The drug was mostly tolerated well with mild or moderate adverse events, including fatigue, nausea, diarrhea, and dry eyes. Only three patients showed thyroid disorder following treatment.

Data Analysis

Despite the positive outcome, it is important to understand that the study was conducted in a very small group of patients. The data shows that 8 out of 15 patients (53%) showed a positive effect. However, treatment with the chemotherapeutic agent is much more effective.

Dr. Konstantin Zakashansky, MD, director of gynecologic oncology at Mount Sinai West, NY, said that with just a single chemo agent, a primary remission rate of 49% to 93% is observed. When given multiple times, the treatment has even shown a cure rate of nearly 100%. Therefore, this study needs further evaluation with a large cohort of patients. Nevertheless, the drug’s safety profile is remarkable in comparison to the chemo. This means that in the future, the drug can be used along with chemo as maintenance therapy. The team is already evaluating the effectiveness of chemo with avelumab in a first-line GTT trial called TROPHAMET in patients who are resistant to chemotherapy.

Howard A. Burris III, MD, president of ASCO, commented, “Given these promising results, as well as reduced toxicity compared to chemotherapy, avelumab deserves further investigation as a potential treatment for these patients.”

Editor: Rajaneesh K. Gopinath

Related Article: ASCO 2020: Maintenance Therapy with Avelumab Post-Chemo Improves Overall Survival of Bladder Cancer Patients

References

1. https://meetinglibrary.asco.org/record/189060/abstract
2. J Clin Oncol 38: 2020 (suppl; abstr LBA6008)

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Author

Ruchi Jhonsa