Patients with soft-tissue sarcoma treated with neoadjuvant immunotherapy had very little residual tumor at the time of surgery and promising long-term survival, according to phase II trial results published by Roland et al in Nature Cancer.
Background
About 13,000 new cases of soft-tissue sarcoma—most commonly dedifferentiated liposarcoma and undifferentiated pleomorphic sarcoma—are diagnosed each year in the United States. Currently, surgery is the only potential cure for those with resectable soft-tissue sarcoma; however, many patients experience cancer recurrence within 5 years. Radiation therapy and chemotherapy prior to surgery are often used to reduce the risk of disease recurrence.
Study Methods and Results
In the recent study, researchers randomly assigned 17 patients with dedifferentiated liposarcoma and 10 patients with undifferentiated pleomorphic sarcoma to receive either neoadjuvant nivolumab or nivolumab with ipilimumab. Following immunotherapy, all of the patients underwent curative-intent surgical resection of their tumors. The researchers collected samples to identify and define clinically meaningful response criteria as well as examine tumor factors that might influence patient outcomes. The researchers found that the presence of intratumoral B cells was associated with improved overall survival.
“Trial participant biopsies were examined at various stages throughout to asses and examine B cells,” explained senior study author Neeta Somaiah, MD, Associate Professor of Sarcoma Medical Oncology at The University of Texas MD Anderson Cancer Center. “We know from previous research the importance of the presence of B cells in a tumor to predict immunotherapy responses, and we found in this study that patients with higher levels of B cells in their tumors were more likely to respond,” she added.
The researchers discovered that following treatment with a combination of immunotherapy and radiation and subsequent surgical removal of the residual mass, 90% of the patients with undifferentiated pleomorphic sarcoma had less than 15% viable tumor cells remaining—an improvement over the amount of residual tumor cells typically seen following radiation alone. Further, the 2-year overall survival rate following neoadjuvant immunotherapy was 90% in the patients with undifferentiated pleomorphic sarcoma and 82% in the patients with resectable retroperitoneal dedifferentiated liposarcoma.
The researchers reported that the patients involved in the study experienced no increased risk of surgical complications and no new side effects, and all of the adverse effects observed were expected and manageable. The most common side effects were rashes, fatigue, and diarrhea.
Conclusions
“These results demonstrate the role immunotherapy treatment can have on soft-tissue sarcomas and how the neoadjuvant treatment platform can help identify novel treatment options for patients,” highlighted lead study author Christina Roland, MD, Associate Professor of Surgical Oncology at The University of Texas MD Anderson Cancer Center. “[Patients with soft-tissue sarcoma] have limited systemic therapy options to consider, and this trial offers data to support the use of immunotherapy in their treatment,” she concluded.
Disclosure: The research in this study was funded by Bristol Myers Squibb. For full disclosures of the study authors, visit nature.com.
