Background: Early-phase trials (EPT), once regarded as a last resort, now provide broad access to therapeutic innovation, with a subset of patients (pts) achieving remarkably durable outcomes.The characteristics of these "long responders" remain poorly defined. Methods:We conducted a retrospective observational study of pts treated in EPT who achieved progression-free survival (PFS) 36 months at Gustave Roussy between June 2008 and December 2023.Clinical, biological, and molecular data were collected, including demographics, prognostic scores (RMH, GRIM, ECOG), tumor type, prior treatments, trial characteristics and outcomes.Results: Among 4,769 pts, 75 (1.6%)achieved PFS 36 months.With a median follow-up of 115 months, median PFS and overall survival (OS) were not reached; 29 deaths occurred.Median age was 59 years; 53% were men (n = 40).Favorable prognostic scores were frequent, with RMH 0-1 in 82% (n = 55), GRIM 0-1 in 85% (n = 53) and ECOG 0-1 in 99% of pts (n=74).Metastatic disease at diagnosis was present in 33% (n = 25), with a median delay of 13 months to EPT inclusion.The most common tumor types were pulmonary adenocarcinoma (23%, n = 17), melanoma (11%, n = 8), acute myeloid leukemia (8%, n = 6), diffuse large B-cell lymphoma, myelofibrosis and bladder urothelial carcinoma (each 5.3%, n=4).Pts received a mean of 2.1 prior treatment lines; 22.6% had 3 lines (n = 17).The most frequent targets were PD-1/PD-L1 (17.3%, n = 13 with n=4 MSI-H pts), RET (9.7%, n = 7), EGFR (8.3%, n = 6), CTLA-4, LAG3, and HDAC (each 6.9%, n=5).Small molecules (58%, n = 48) and monoclonal antibodies (35%, n = 25) predominated.Among solid tumors (78.6%, n = 59), best response was complete response in 49.1% (n = 29), partial response in 38.9% (n = 23), and stable disease in 11.8% (n = 7); durable CR was maintained in 69% of complete responders (n = 20). Conclusions:This cohort demonstrates that a small but significant proportion of pts in EPT achieve long-term survival.Favorable prognostic scores, access to targeted and immune-based therapies contributed to durable benefit.These findings highlight the range of precision medicine and the ability of EPT to induce long-lasting clinical benefit in a pre-treated population.
Diagne et al. (Wed,) studied this question.