Targeted therapy and immunotherapy improve outcomes in rare thyroid cancer

The trial enrolled 42 patients across three cohorts to evaluate mutation-matched targeted therapy and the immune checkpoint inhibitor atezolizumab. The median OS across all cohorts was 19 months, which compares favorably to historical OS of five months for patients with ATC. The longest OS among the cohorts was 43.2 months in patients with BRAFV600E mutations – the longest OS published to date for systematic therapy in ATC.

Anaplastic thyroid carcinoma is a rare and highly aggressive malignant tumor with a very poor prognosis. ATC often develops from differentiated thyroid cancer subtypes, such as papillary and follicular thyroid carcinoma, and each subtype has distinct driver mutations that can influence tumor behavior and progression.

Mutations in BRAF have therapeutic and prognostic implications and are seen in 40% of thyroid cancer patients. The trial enrolled 18 patients with BRAF-mutated ATC in cohort 1, who received treatment with atezolizumab plus the targeted therapy combination of vemurafenib and cobimetinib. The median OS was 43.2 months with an objective response rate (ORR) of 50%.

Cohort 2 enrolled 21 patients with RAS (NRAS, KRAS or HRAS) or NF1/2 mutations for treatment with cobimetinib plus atezolizumab. The combination achieved a median OS of 8.7 months and a 14% ORR.

The researchers observed side effects that were expected based on previous trials with these drugs. Among the most common adverse events for all cohorts were fatigue, lymphopenia, diarrhea and anemia. There were notable serious side effects in a few patients, including colonic and esophageal perforations.

The study was supported by Genentech, MD Anderson's Rare Tumor Initiative as part of the institution's STrategic Research Initiative DEvelopment (STRIDE) program, and by the National Institutes of Health (CA016672).

Source:

University of Texas M. D. Anderson Cancer Center

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