(UroToday.com) The 2024 American Society of Clinical Oncology Genitourinary (ASCO GU) cancers symposium held in San Francisco, CA between January 25th and 27th was host to a renal cell, adrenal, penile, urethral, and testicular cancers poster session. Dr. Renee Maria Saliby presented the results of an International Metastatic renal cell carcinoma Database Consortium (IMDC) analysis evaluating intermediate endpoints for overall survival in metastatic renal cell carcinoma (RCC) treated with immune checkpoint inhibitors (ICIs).
In phase 3 trials, the assessment of the overall survival primary endpoint requires an extended follow-up period and, a large number of events, and is associated with exponentially increasing costs. As such, validated, surrogate endpoints in the RCC disease space are sorely needed. The objective of this study was to determine whether shorter-term/intermediate endpoints such as time to treatment failure (TTF) and time to next therapy (TTNT) are significantly correlated with overall survival in patients receiving 1st line ICI-based therapy.
This analysis included all patients from the IMDC database who received contemporary, guidelines recommended 1st line ICIs between 2013 and 2023. The endpoints were defined as follows:
- TTF: From ICI start to drug cessation or death
- TTNT: From ICI start until initiation of next treatment line or death
- OS: Defined from ICI start
From a statistical modeling standpoint, the hazard ratios for overall survival were calculated using Cox regression modeling with the main predictors of interest defined as 6-months TTF and TTNT event status, adjusting for known confounders, including:
- IMDC risk groups
- Presence of bone, brain, or liver metastases
- Histology
- Age
- Prior nephrectomy
- ICI type and year of ICI start
Endpoint correlations across all follow-up times of individual patient data were performed using Kendall’s Tau correlation with a Clayton copula.
The study cohort was comprised of 1,667 patients with a median follow-up of 15.4 months (IQR: 7.1 – 28.6). The median age at the start of 1st line treatment was 63 years (IQR: 56 – 70). 73% of patients were male.
On multivariable Cox regression modeling, TTNT (HR: 2.82, 95% CI: 2.22 to 3.59) outperformed TTF (HR: 2.74, 95% CI: 2.15 to 3.49). Furthermore, TTNT outperformed TTF with regard to Kendall’s Tau correlation with overall survival (0.67 versus 0.49).
Dr. Saliby and colleagues thus concluded that time to next therapy has the strongest association with overall survival making it a potentially clinically meaningful intermediate endpoint for evaluating treatment efficacy in immune checkpoint inhibitor-treated patients. Future analysis will require validation of these surrogate outcomes using clinical trial data.
Presented by: Renee Maria Saliby, MD, MSc, Research Fellow,| Dana-Farber Cancer Institute, Boston, MA
Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2024 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, San Francisco, CA, January 25th – January 27th, 2024