101P - Progression-Free Survival is an acceptable surrogate endpoint for chemo-immunotherapy combinations in Cervical Carcinoma, an EORTC Young GCG study

Background

Immunotherapy has become a standard of care for recurrent and metastatic cervical carcinoma resulting in the need to carefully assess for surrogacy focusing on new therapeutic scenarios. This study delves into a systematic review and meta-analysis to unravel the potential of progression-free survival (PFS) as a surrogate endpoint in cervical cancer.

Methods

We performed a comprehensive search of randomized phase 2 and 3 clinical trials in advanced and recurrent cervical cancer. PRISMA guidelines were followed, and the study was registered in PROSPERO (CRD42023405604). Inclusion criteria required RCTs with mature PFS and OS data. Trials with adjuvant treatment or disease-free survival as primary endpoint were excluded. Subgroup analysis was performed by type of treatment (i.e. chemotherapy-based, chemo-immunotherapy combinations).

Results

11,348 articles were screened, and 31 included in the final analysis. In the overall population, a robust correlation between PFS and OS was observed (Spearman's rho = 0.66, p-value < 0.001). We calculated the Surrogate Threshold Effect (STE) at the PFS intersection with null OS outcome (p = 0.05), resulting in a threshold for PFS z-score (z-PFS) of 2.23. When examining the results by treatment modality, chemotherapy trials exhibited a notably weak and non-significant correlation (Spearman 0.34, p = 0.31) with a significantly higher STE (z-PFS = 2.92). Conversely, in chemo-immunotherapy combinations, the correlation was notably robust and statistically significant (Spearman 0.94, p = 0.017), associated with a considerably lower STE (z-PFS = 2.1).

Conclusions

PFS may serve as a surrogate endpoint in cervical cancer. Notably, PFS was a more promising surrogate marker in the context of chemo-immunotherapy when compared to chemotherapy alone. This aligns with the hypothesis that chemo-immunotherapy induces a response, which is further sustained through maintenance immunotherapy, thereby enabling PFS to better capture the impact on OS. Conversely, in chemotherapy-based treatments, the expected survival benefit may be more limited, and PFS may not as strongly capture the effect of chemotherapy alone.

Legal entity responsible for the study

European Organisation for Research and Treatment of Cancer (EORTC), Young Gynaecological Cancer Group.

Funding

Has not received any funding.

Disclosure

F. Herrera: Financial Interests, Institutional, Research Grant, Grant/Research Support: Accuracy Inc, Bioprotext, BMS, Roche-ImFlame/ImCore, Nanobiotix, AstraZeneca, Eisai, MSD, Seagen; Financial Interests, Institutional, Research Grant, Grant/Research Support Foundations: Prostate Cancer Foundation, San Salvatore Foundation; Financial Interests, Personal, Advisory Board, Consultation, fees, travel expenses: Johnson & Johnson, Seagen, MSD, BMS, AstraZeneca, Eisai; Non-Financial Interests, Institutional, Non-financial benefits, Academic Collaborations: EORTC chairman GCG, ESMO Scientific Committee member for drug development, ASTRO Scientific Committee Annual Meeting. A. Madariaga Urrutia: Financial Interests, Personal, Invited Speaker: GSK, AstraZeneca, Clovis, MSD; Financial Interests, Personal, Advisory Board: GSK, AstraZeneca, PharmaMar. All other authors have declared no conflicts of interest.