Adjuvant Pembrolizumab after Upfront Multimodal Therapy for Stage IVB Anaplastic Thyroid Cancer.

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. 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). 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 ( = 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] ( = 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. 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.