Adjuvant pembrolizumab after upfront multimodal therapy for stage IVB Anaplastic Thyroid Cancer
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Background
ATC has historically been almost uniformly fatal. In patients with 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 ( NCT05059470 ) that closed early due to poor accrual, and a retrospective cohort of consecutive patients who received adjuvant pembrolizumab and mirrored 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. The secondary objective was median overall survival (OS). Descriptive statistics and Kaplan-Meier method for survival analysis were used.
Results
Between March 2020 and February 2024, 16 patients were treated with adjuvant pembrolizumab. The control arm included 16 patients. The median age in both groups was 59 years. The median PDL1 score and tumor mutation burden in the adjuvant pembrolizumab arm were 50% (range, 0-95%) and 3 mut/Mb (range, 0.5-29). There were more RAS mutated patient tumors in the adjuvant arm (40%) compared to the historical control group (18%). The majority, 14/16 (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 (95%CI 2.04-16.20), respectively (p=0.006; HR 0.24 (95%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 (95%CI 13.9, NA) (p = 0.009; HR 0.11 (95%CI: 0.01, 0.83)). The 12-and 24-month survivals were 80% (95%CI 0.51-0.93) and 52% (95%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.
