Neoadjuvant immunotherapy may improve sarcoma outcomes
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A phase 2 trial conducted by researchers at The University of Texas MD Anderson Cancer Center demonstrated the safety and potential efficacy of neoadjuvant immunotherapy for patients with soft tissue sarcoma.
The study — results of which were published in Nature Cancer — evaluated neoadjuvant nivolumab (Opdivo, Bristol Myers Squibb) or nivolumab with ipilimumab (Yervoy, Bristol Myers Squibb) for 17 adults with resectable retroperitoneal dedifferentiated liposarcoma and 10 adults with undifferentiated pleomorphic sarcoma.
After completion of immunotherapy, all patients underwent surgery to remove their tumors. The researchers collected samples to identify and characterize clinically meaningful response criteria. They also used the samples to assess tumor factors that might affect outcomes.
“Our findings provide evidence that neoadjuvant checkpoint blockade in combination with radiotherapy in undifferentiated pleomorphic sarcoma is safe with significant pathological responses and a promising survival benefit,” Christina L. Roland, MD, MS, FACS, associate professor of surgical oncology at The University of Texas MD Anderson Cancer Center, told Healio. “Neoadjuvant checkpoint blockade in dedifferentiated liposarcoma and undifferentiated pleomorphic sarcoma is associated with complex immune changes in the tumor microenvironment, including stimulation of tertiary lymphoid structures and B cells, and disruption of associations between B cells and regulatory T cells.”
Healio spoke with Roland about the rationale for this study, as well as the potential implications of the findings for treating the approximately 13,000 cases of soft tissue sarcoma diagnosed in the United States each year.
Healio: What did you hope to learn from the study?
Roland: We were interested in evaluating the role of immunotherapy before surgery for patients with localized, resectable retroperitoneal dedifferentiated liposarcoma and extremity/truncal undifferentiated pleomorphic sarcoma based on data that checkpoint blockade was effective in the metastatic setting.
Healio: What did you find?
Roland: Pathologic response served as the primary endpoint of the trial. Ninety percent of patients with undifferentiated pleomorphic sarcoma had less than 15% viable tumor cells remaining — higher than what has historically been seen with radiation alone. The OS rate at 2 years after first treatment was 82% in resectable retroperitoneal dedifferentiated liposarcoma and 90% in undifferentiated pleomorphic sarcoma.
Healio: How did the results from this cohort compare with historical results of patients who did not undergo neoadjuvant immunotherapy?
Roland: Historic data from our institution of preoperative radiation therapy in 17 extremity/truncal undifferentiated pleomorphic sarcomas demonstrated a median hyalinization of 17.5% and a pathologic complete response rate of 9%. In our study, the median hyalinization was 89%.
Healio: What are the implications of these findings? Are they sufficient to change the standard of care?
Roland: Further studies are needed to optimize these regimens, determine the long-term benefits, and fully elucidate the mechanisms of response and resistance. Across tumor types, neoadjuvant immune-checkpoint blockade trials have shown increased activity, and these trial designs have gained a lot of attention, suggesting that immune-checkpoint blockade may be more effective in the earlier localized setting than in the advanced metastatic setting.
Healio: Is there anything else you’d like to mention?
Roland: Another important aspect of this trial was the systematic collection of biopsies pretreatment, on treatment and at the time of surgery. We know from previous research the importance of the presence of B cells in a tumor to predicting responses to immunotherapy. In this study, we found that patients with higher levels of B cells in their tumors were more likely to respond.
References:
- Roland CL, et al. Nat Cancer. 2024;doi:10.1038/s43018-024-00726-z.
- The University of Texas MD Anderson Cancer Center. Immunotherapy before surgery leads to promising long-term survival in sarcoma patients (press release). Available at: https://www.mdanderson.org/newsroom/immunotherapy-before-surgery-leads-to-promising-long-term-survival.h00-159695178.html. Posted Feb. 13, 2024. Accessed Feb. 23, 2024.
For more information:
Christina L. Roland, MD, MS, FACS, can be reached at The University of Texas MD Anderson Cancer Center, 1400 Pressler St., Houston, TX 77030; email: clroland@mdanderson.org.
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