Anti–Programmed Death Ligand 1 Plus Targeted Therapy in Anaplastic Thyroid Carcinoma
Authors: Cabanillas Maria E. , Dadu Ramona , Ferrarotto Renata , Gule-Monroe Maria , Liu Suyu , Fellman Bryan , Williams Michelle D. , Zafereo Mark , Wang Jennifer R. , Lu Charles , Ning Matthew , McKinley Brian A. , Woodman Scott E. , Duose Dzifa , Gunn Gary B. , Busaidy Naifa L. ,   Rare Tumor Initiative Team, Alrawi Ahmed N , Arrechedera Claudio A , Ayers Kimberly S , Bedoya Caludia A , Burton Elizabeth , Chon Connie A , Chu Randy A , Crosby Shadarra D , Do Jonathan , Lima Cibelle FP , Szu-Chin Fu , Futreal Andy , Garcia Ana L , Garica-Prieto Celia , Gite Swati , Gumbs Curtis , Hargraves Kristin J , He Meng , Horombe Chacha , Ibarguen Heladio P , Jackson Stacy , Jacob Jeena J , Jiang Mei , Khanduri Isha , Kinyua Walter K , Knafl Mark , Lang Wenhua , Little Latasha D , Lu Wei , Mallampati Saradhi , Mendoza Mary GT , Meric-Bernstam Funda , Mohammad Mohammad M , Piubelli Mario LM , Prabhakaran Sabitha , Shaw Kenna R , Song Xiaofei , Subramanya Sandesh , Sun Baohua , Virani Shumaila , Wang Wanlin , Wistuba Ignacio , Woodman Scott E , Xu Mingchu , Zhang Jianhua , Zhang Qingxiu C , Zhang Shanyu 
Published: October 2024

ImportanceAnaplastic thyroid carcinoma (ATC) is a rare and lethal cancer. Although progress has been made in recent years in patients with mutated BRAF tumors, those who respond initially eventually die of their disease; furthermore, there are no approved therapies for non-BRAF mutated tumors.ObjectiveTo determine whether treatment with matched-targeted therapy plus immune checkpoint inhibitors were associated with improved overall survival (OS).Design, Setting, and ParticipantsA phase 2 trial at a single center, tertiary institution with parallel cohorts, assigning treatment with targeted therapy according to the tumor mutation status. Patients with mutated BRAF V600E tumors received vemurafenib/cobimetinib plus atezolizumab (cohort 1); those with mutated RAS (NRAS, KRAS, or HRAS) or NF1/2 tumors received cobimetinib plus atezolizumab (cohort 2). Patients without any of these variants were assigned to receive bevacizumab plus atezolizumab (cohort 3). Patients were enrolled from August 3, 2017, to July 7, 2021. All consecutive, systemic therapy-naive patients with ATC with active disease and who met eligibility criteria were considered for participation. The analysis was conducted in September 2023.InterventionsPatients were assigned to targeted therapy based on the driver mutation as follow: BRAF V600E (cohort 1, vemurafenib plus cobimetinib), RAS/NF (cohort 2, cobimetinib), or non-BRAF/RAS/NF (cohort 3, bevacizumab). All received atezolizumab.Main Outcomes and MeasuresThe primary outcome of the study was median OS of the entire targeted therapy cohort, compared with historical median OS of 5 months.ResultsForty-three patients with ATC were enrolled in the targeted therapy cohorts, of which 42 were included in the primary analysis. The median OS in patients across these 3 cohorts was 19 months (95% CI, 7.79-43.24). Median OS and progression-free survival per cohort were as follows: cohort 1: 43 months (95% CI, 16-not estimable [NE]), 13.9 months (6.6-64.1); cohort 2: 8.7 months (95% CI, 5.1-37.0) and 4.8 months (1.8-14.7); cohort 3 (vascular endothelial growth factor inhibitor group): 6.21 months (4.1-NE) and 1.3 months (1.3-NE), respectively.Conclusions and RelevanceIn this nonrandomized clinical trial, atezolizumab combined with targeted therapy resulted in a longer median OS than historical landmark, achieving the study’s primary end point, with cohort 1 achieving the longest OS.Trial RegistrationClinicalTrials.gov Identifier: NCT03181100