Atezolizumab/Matched-Targeted Therapy Improves OS in Anaplastic Thyroid Cancer
Patients with anaplastic thyroid cancer had a significant boost to overall survival with atezolizumab and targeted therapy.
Patients with anaplastic thyroid cancer had a significant boost to overall survival with atezolizumab and targeted therapy.
Atezolizumab (Tecentriq) combined with targeted therapy, including vemurafenib (Zelboraf) plus cobimetinib (Cotellic), or bevacizumab (Avastin) resulted in longer median overall survival (OS) in patients with anaplastic thyroid carcinoma (ATC) than historical landmarks, according to a phase 2 trial (NCT03181100) published in JAMA Oncology.
Patients enrolled in the trial were split into 3 cohorts: cohort 1 for patients with mutated BRAF V6OOE tumors who received vemurafenib/cobimetinib plus atezolizumab; cohort 2 for patients with mutated RAS or NF1/2 tumors who received cobimetinib plus atezolizumab; and cohort 3 for patients without any of these variants who received bevacizumab plus atezolizumab.
Across all 3 cohorts, the median OS was 18.23 months (95% CI, 7.79-43.24) and the median follow-up time was 18.97 months (95% CI, 0.43-72.11). For cohort 1 (n = 19), the median OS and progression-free survival (PFS) was 43.24 months (95% CI, 16-not estimable [NE]) and 13.93 months (95% CI, 6.60-64.13). For cohort 2 (n = 21), they were 8.74 months (95% CI, 5.13-36.96) and 4.80 months (95% CI, 1.84-14.69). For cohort 3 (n = 3), they were 6.21 months (95% CI, 4.1-NE) and 1.3 months (95% CI, 1.3-NE), respectively. The median follow-up time for cohorts 1 and 2 were 42.14 months (95% CI, 2.66-72.11) and 8.74 months (95% CI, 0.43-55.92), respectively.
“The genetically-matched targeted therapy plus immunotherapy combination strategy across cohorts 1 to 3 resulted in an OS of 19 months—to our knowledge the longest OS reported to date in an [anaplastic thyroid carcinoma] clinical trial, achieving the primary objective of the study,” the authors of the study noted.
A total of 43 patients were enrolled, and 42 were evaluable for the study. To be eligible for entry, an ECOG performance status of 0 to 2, as well as adequate organ function, were required. Patients who received anti-PD1 or PD-L1 antibodies or pathway-targeting agents were excluded, while patients with prior cancer history were not excluded due to the nature of anaplastic thyroid cancer. At the time of the data cutoff, 29 patients had died, leaving 13 alive.
Before treatment, an induction phase of paclitaxel at 80 mg/m2 or nab-paclitaxel at 125 mg/m2 was administered weekly, for up to 3 doses, to ease into mutation-driven treatment assignment.
Patients who had sufficient results due to therapy were allowed to forego radiation in their surgery to control their locoregional disease during the trial.
Adverse effects (AEs) were noted across all cohorts. There was 1 death possibly caused by trial participation that was due to colonic perforation in cohort 1. Other serious AEs were colitis, papilledema because of nerve neuritis, retinopathy, left ventricular dysfunction/decreased ejection fraction, pneumonitis, pancreatitis, and esophageal perforation.
The primary end point was median OS, and the secondary points were the overall response rate (ORR) and PFS. ORR for cohort 1 was 50%, cohort 2 was 14%, and cohort 3 was 33%. A complete response of 5.6% was only noted in cohort 1. In cohorts 1 to 3, 20 patients were alive 2 years in and 15 patients with anaplastic thyroid carcinoma had to receive treatment for longer than 12 months.
A result of the trial is that, of 12 patients with locoregional tumors that became resectable during treatment, 11 opted to undergo surgery, and 8 of them are still alive. Of these cases, 4 were stage IVB and 8 were stage IVC. As a result of the surgery, 2 patients required temporary tracheostomies and/or postoperative radiation.
The authors of the study emphasize that their entry criteria were more permissive, something they chose to do because of the historical challenges of anaplastic thyroid cancer trials have had attempting to gather enough participants. For this reason, patients who could not swallow pills were allowed to crush vemurafenib or substitute for cobimetinib, and the trial also permitted bridging chemotherapy.
Reference
Cabanillas ME, Dadu R, Ferrarotto R, et al. Anti–programmed death ligand 1 plus targeted therapy in anaplastic thyroid carcinoma: a nonrandomized clinical trial. JAMA Oncol. Published online October 24, 2024. doi:10.1001/jamaoncol.2024.4729
