Background: Anaplastic thyroid cancer (ATC) has historically been almost uniformly fatal. In patients with the loco-regional disease (stage IVB), multimodal therapy (upfront surgery when feasible, radiation +/- concurrent chemotherapy) followed by observation is the current standard of care. Methods: Stage IVB ATC patients treated with multimodal therapy, followed by adjuvant pembrolizumab were studied. Data were combined from a prospective, phase 2 trial that closed early due to poor accrual, and a retrospective cohort of consecutive patients who received adjuvant pembrolizumab, mirroring the trial eligibility criteria. Patients received adjuvant pembrolizumab starting within 6 weeks after completion of radiation. An age and treatment-matched control arm treated with multimodal therapy without adjuvant pembrolizumab was selected for comparison. The primary objectives included median progression-free survival (PFS) and recurrence rate, and the secondary objective was median overall survival (OS). Results: Sixteen patients were included in each arm. The median age in both groups was 59 years. The median PDL1 score in the adjuvant pembrolizumab arm was 50% (range, 0-95%). The majority (88%) had upfront surgery in both groups. The median follow-up time was 24.3 months in the adjuvant arm and 56.7 months in the control arm. The median PFS in the adjuvant and control arm was not reached, and 5.4 months [CI: 2.04-16.20], respectively (p = 0.006; HR 0.24 [CI: 0.08, 0.73]). The median OS was not reached in the adjuvant pembrolizumab group. In the control group, the median OS was 31 months [CI: 13.9, NA] (p = 0.009; HR 0.11 [CI: 0.01, 0.83]). The 12-and 24-month survival rates were 80% [CI: 0.51-0.93] and 52% [CI: 0.25-0.74], respectively, in the control arm, whereas all patients in the adjuvant arm were still alive at 1- and 2-years. Conclusion: Adjuvant pembrolizumab appears to be a safe and effective strategy to prevent recurrences and prolong survival in stage IVB ATC patients following multimodal therapy. Confirmatory studies are needed.
Keywords: chemotherapy; immunotherapy; locoregional disease; radiation; undifferentiated.