(UroToday.com) The 2024 American Society of Clinical Oncology (ASCO) Annual Meeting held in Chicago, IL between May 31st and June 4th, 2024 was host to a kidney and bladder rapid oral abstract session. Dr. Sahil Doshi presented the results of a multi-institutional analysis of outcomes with first-line systemic therapy for 102 patients with metastatic chromophobe renal cell carcinoma (RCC). Chromophobe RCC accounts for 5–10% of all RCCs. Given the relative rarity of this disease, there is limited clinical trial data to guide systemic therapy for metastatic chromophobe RCC disease. Accrual of such patients in these trials has been limited historically, as summarized in the table below:
To this end, Dr. Doshi and colleagues conducted a retrospective analysis from three centers (MSKCC, MDACC, Johns Hopkins) of metastatic chromophobe RCC patients receiving 1st line systemic therapy. They calculated time to treatment failure and overall survival using the Kaplan-Meier method. The median time-to-event was reported for each treatment category, and these categories were compared using the log-rank test. Best response rates were assessed using the RECIST criteria. Patients were grouped into one of four categories based on the 1st line treatment received:
- Monotherapy targeted agents (TKI or mTORi; n=57)
- Doublet therapy with two targeted agents (VEGFi/TKI + mTORi; n=14)
- Doublet therapy with targeted agent + immunotherapy (TKI + IO; n=17)
- Immunotherapy alone (IO monotherapy or IO + IO; n=14)
The baseline patient characteristics are summarized below. The median patient age at diagnosis was 56 years, and 61% were males. 93% of patients had undergone a prior nephrectomy. 30% of patients had de novo metastatic disease, and 30% also had sarcomatoid features. Two-thirds of patients had 1–2 sites of metastases. 69% of patients had IMDC favorable- or intermediate-risk disease.
The most commonly received 1st line therapy was single agent targeted therapy with either a TKI or mTORi (55%). These patients also had the longest median follow-up in this cohort (45 months). This reflects the study inclusion period of 2006 to 2023, with many such patients having received this class of therapy between 2006 and 2018.
There were significant differences in time to treatment failure between the four treatment groups (log-rank p=0.034). The median time to treatment failure was longest for patients receiving VEGF/TKI + mTORi doublet therapy (17 months) and TKI + IO doublet therapy (15 months).
From an overall survival standpoint, the median survival was similarly longest for patients in the VEGF/TKI + mTORi doublet therapy (99 months) and TKI + IO doublet therapy groups (56 months).
The waterfall plot below depicts the best objective response by treatment received.
When analysis was stratified by number of agents received (i.e., targeted monotherapy versus doublets containing targeted therapies), patients receiving doublet therapies (TKI + IO or VEGFi/TKI + mTORi) had superior median time to treatment failure (15 versus 5 months) and overall survival (56 versus 23 months).
Dr. Doshi concluded as follows:
- Metastatic chromophobe RCC has limited prospective evidence for optimal systemic therapy selection.
- This retrospective analysis demonstrates improved clinical outcomes with doublet therapies as compared to single-agent regimens.
- The investigators are expanding their efforts and collaborating with additional cancer centers to increase their patient cohort and make comparisons with more contemporary regimens feasible.
Presented by: Sahil Doshi, MD, Medical Oncology/Hematology Fellow at Memorial Sloan Kettering Cancer Center, New York, NY
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 (ASCO) Annual Meeting, Chicago, IL, Fri, May 31 – Tues, June 4, 2024.