A Non-randomized Phase 2 Trial of Pembrolizumab in Untreated Patients with Carcinoma of Unknown Primary Site
Mené sur 33 patients atteints d'un carcinome d'origine primitive inconnue, cet essai multicentrique de phase II non randomisé évalue l'efficacité, du point de vue du taux de réponse objective, et la toxicité du pembrolizumab
Background: Carcinoma of unknown primary (CUP) is a heterogeneous group of cancers with no identifiable primary lesion, but metastatic epithelial disease. The diagnosis portends a poor prognosis with limited systemic therapy options. Researchers hypothesize that these primary lesions are occult, in part, due to anti-cancer immune surveillance.
Methods: This was a non-randomized, multi-center phase 2 trial of pembrolizumab administered at 200 mg intravenously every 3-weeks in patients with untreated CUP. The primary endpoint was measuring safety and objective response rate (ORR). Secondary objectives included progression free survival (PFS) and overall survival (OS).
Results: In total 33 patients were enrolled and 27 were evaluable. The median age was 64 (range 21-80), the majority were male (57.6%) and ECOG 1 (84.8%). There were no new signals of toxicity. The ORR was 11.1% (95% CI 2.35 - 29.16%) and disease control rate was 51.9% as per RECIST criteria. The median PFS and OS were 2.98 (95% CI 2.07 - 4.63) and 9.49 (95% CI 3.84 - 14.72) months respectively. The one patient who developed a complete response had mismatch repair (MMR) deficiency and has completed 2 years of therapy. Of the 2 patients with a partial response, one had an MMR proficient tumour, while the remaining 1 had unknown MMR status. Higher PD-L1 score was associated with response to pembrolizumab.
Conclusions: This is the first study investigating the safety and efficacy of pembrolizumab in untreated CUP patients. Some responses were observed, but this primary endpoint was not met. We recommend screening all CUP patients for MMR/microsatellite instability (MSI). Future studies should evaluate combination therapies with pembrolizumab.
European Journal of Cancer , résumé, 2026