Pembrolizumab (PD-1) + Docetaxel/Doxorubicin Delivers Modest Responses in Advanced Salivary/Thyroid Cancers

Pembrolizumab is an anti–PD-1 immune checkpoint inhibitor combined here with cytotoxic chemotherapy (docetaxel or doxorubicin) in the single-center, parallel-cohort iPRIME study (Phase 2–like design; NCT03360890) for unresectable/metastatic salivary gland cancers (n=27) and thyroid cancers (n=12) treated 2018–2022, followed by pembrolizumab maintenance (with optional chemo rechallenge at progression). In salivary cancers, ORR was 25.6% (7/27) with DCR 89% and median PFS 8.6 months; adenoid cystic carcinoma (ACC) ORR was 27% (4/15) with median PFS 8.0 months, and OS did not differ between ACC vs non-ACC (p=0.26). These outcomes look broadly in the range of historical systemic options—pembrolizumab monotherapy in PD-L1+ salivary gland carcinoma reported ORR ~12% in KEYNOTE-028, while platinum–taxane chemo regimens have reported ORRs ~40%+ with mPFS ~8–9 months in mixed salivary populations—yet toxicity here included Grade 4 events (9 patients) and one Grade 5 event, tempering enthusiasm for a “synergy” claim.