Articles related to IMMUNOTHERAPY

Meaningful advances in sarcoma treatment have been painfully slow. Modern immunotherapy may change that. The article referenced by this editorial reports the results of CMB305 plus atezolizumab or atezolizumab alone in patients with NY-ESO-1–expressing synovial or myxoid round cell liposarcoma. The relevance of this study furthers the data using novel immunotherapeutic strategies, which generate B- and T-cell responses for two rare sarcomas that can serve as a foundation for future trials.

Combining BCG with N-803 “results in significant complete response rates and long-term disease-free rates without significant systemic side effects,” reported lead study investigator Sam S. Chang, MD, of Vanderbilt University Medical Center. N-803 is a high affinity, interleukin 15 immunostimulatory fusion protein that promotes the proliferation and activation of natural killer cells and CD8+ T cells without binding to regulatory T cells. Its use in this phase two/three study including 83 patients with CIS and 77 with papillary NMIBC. In the CIS group, the complete response rate was 71% with a median duration of response of 23.6 months. NMIBC group had 12- and 24-month disease-free survival (DFS) rates of 57% and 48%, respectively. The median DFS was 23.6 months. In both groups, cystectomy was avoided in more than 90% of patients.

A potentially practice-changing clinical trial for first line therapy is the first to show that the combination of two immunotherapy medications is an effective treatment for hepatocellular carcinoma (HCC). The HIMALAYA study evaluated combination immunotherapy (IO-IO), durvalumab with tremelimumab, as frontline therapy in patients with unresectable HCC. Overall survival was significantly improved with the IO-IO combination compared with sorafenib monotherapy (16.4 vs 13.8 months; hazard ratio [HR], 0.78; 96% CI, 0.65-0.92; P =.0035). Early results of the phase three LAUNCH trial are also promising. This trial compared the combination of lenvatinib with transarterial chemoembolization (TACE) to lenvatinib alone in an Asian population with advanced HCC. The lenvatinib-TACE group achieved a higher median overall survival (17.8 vs. 11.5 months and median progression-free survival (10.6 vs. 6.4 months). Muhammad Shaalan Beg, MD, director for GI Medical Oncology at UT Southwestern Medical Center in Dallas summarizes these and other takeaways from emerging research on advanced HCC presented at the recent ASCO GI Symposium.

In a randomized clinical trial of 128 patients with refractory mCRC, the addition of the PD-L1 inhibitor atezolizumab to capecitabine and bevacizumab therapy resulted in marginally longer PFS vs the placebo comparator arm. However, the median improvement — 4.4 vs 3.6 months – was deemed not clinically relevant.

This update on the PACIFIC trial comparing durvalumab with placebo in patients with unresectable, stage III non–small-cell lung cancer demonstrated robust and sustained OS and durable PFS benefit. The updated, exploratory analyses of survival, approximately 5 years after the last patient was randomly assigned demonstrate robust and sustained OS and durable PFS benefit with durvalumab after chemoradiotherapy. An estimated 42.9% of patients randomly assigned to durvalumab remain alive at 5 years and 33.1% of patients randomly assigned to durvalumab remain alive and free of disease progression. These results establish a new benchmark for standard of care in this setting.

Interest in immune-modulating neoadjuvant therapy for melanoma is growing. It is possible that BRAF/MEK inhibition will be more effective in the neoadjuvant than in the adjuvant setting because of the effect of the tumor biomass. And the benefits neoadjuvant therapy would offer in assessing biologic response assessment to treatment are significant. In this review the authors discuss the rationale for this treatment approach, summarize completed and ongoing neoadjuvant clinical trials, and contextualize these findings within the growing body of knowledge about targeted and immune checkpoint therapy.