(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 cancers poster session. Dr. Michael Atkins presented a subgroup analysis of the phase II LITESPARK-013 trial of belzutifan in patients with advanced clear cell renal cell carcinoma (ccRCC).
The first-in-class oral hypoxia-inducible factor-2α inhibitor belzutifan is approved in the United States at a dose of 120 mg once daily (QD) for certain patients with von Hippel-Lindau disease and for patients with advanced renal cell carcinoma (RCC) following treatment with a programmed cell death protein 1 (PD-1) or programmed cell death ligand (PD-L1) inhibitor and a vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI).1
The randomized phase 2 LITESPARK-013 study (NCT04489771) was designed to determine whether belzutifan 200 mg QD demonstrates an improved therapeutic index compared to the 120 mg QD dose in a large sample of patients with pre-treated advanced clear cell RCC:
- Comparable efficacy was observed between the 200 mg (n = 78) and 120 mg (n = 76) arms
- Objective response rate (ORR): 23.1% versus 23.7% (1-sided p=0.53)
- Duration of response (DOR): median of 16.1 months versus not reached
- Progression-free survival (PFS): median of 9.1 months versus 7.3 months (HR: 0.94, 95% CI: 0.63–1.40, 1-sided p-value=0.39).
The objective of this study was to present a post hoc efficacy analysis in the pooled population of LITESPARK-013 (200 mg and 120 mg arms) across patient subgroups based on prior therapy, International Metastatic RCC Database Consortium (IMDC) risk group, and baseline disease characteristics.
End points of this post hoc analysis were ORR, DOR, and PFS per RECIST v1.1 by blinded independent central review (BICR). 95% CIs for ORR were determined based on the binomial exact method. DOR and PFS 95% CIs were estimated using the Kaplan-Meier method. No formal hypothesis testing was performed.
The pooled study population included 154 patients (200 mg arm, n = 78; 120 mg arm, n = 76). At the data cutoff date of February 10, 2023:
- 39 patients (25.3%) remained on treatment.
- 115 patients (74.7%) had discontinued study treatment because of:
- Progressive disease (53.2%)
- Adverse events (9.7%)
- Clinical progression (7.1%)
- Patient withdrawal (3.2%)
- Physician decision (1.3%)
The median time from randomization to the data cut-off date was 20.1 months (range, 14.8–28.4). The baseline patient characteristics are summarized below. The median patient age was 64 years. 83% had IMDC intermediate- or poor-risk disease. 48% had received 1 prior line of therapy, and 52% had received 2–3 prior lines of therapy. 51% had received 1 prior TKI and 20% had received 2–3.
As of the data cutoff date, 39 patients (25.3%) in the pooled population remained on treatment. The median follow-up was 20.1 months (range, 14.8–28.4). In the pooled population, the ORR was 23.4% (4 complete responses, 32 partial responses), the median duration of response was 16.1 months, and the median PFS was 7.9 months. Efficacy outcomes by prior lines of therapy, prior regimen received, number of prior TKI regimens, choice of 1st line therapy, IMDC risk group, and presence/absence of sarcomatoid differentiation are summarized below:
The confirmed ORRs are illustrated in the bar graphs below. ORRs were superior for patients following:
- 1 prior line of therapy: 25% (versus 17% for 2–3 prior lines)
- Prior IO-only therapy: 27% (versus 17-20% post-IO/VEGF)
- No prior TKI: 27% (versus 19% and 16% post- and 2-3 prior TKIs)
- 1st line IO only: 35% (versus 19% post-1st line IO + TKI)
- Favorable risk disease: 30% (versus 22% for intermediate/poor-risk)
- No sarcomatoid differentiation: 24% (versus 5.6% for those with sarcomatoid differentiation)
Kaplan-Meier estimates of progression-free survival are summarized below, with subgroup survival trends mirroring those observed for ORRs:
Dr. Atkins concluded as follows:
- In this post hoc analysis from LITESPARK-013, durable antitumor responses were observed across subgroups in the pooled population of patients with advanced clear cell RCC who were treated with belzutifan at doses of 200 mg QD or 120 mg QD.
- Results should be interpreted with caution given the post hoc nature of the analysis, potential imbalances when pooling across both arms and the small sample size of some subgroups, leading to wide ORR or PFS 95% CIs.
- These results suggest that belzutifan is an effective treatment option for pretreated advanced RCC across various subgroups.
- Additional research may further elucidate the activity of belzutifan in selected patient populations, such as those in the favorable IMDC risk group and/or those who have received fewer prior therapies.
Presented by: Michael B. Atkins, MD, FASCO, Deputy Director, Georgetown Lombardi Comprehensive Cancer Center, Scholl Professor and Vice Chair of the Department of Medical Oncology, Georgetown University Medical Center, Washington, DC
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, May 31st – June 4th, 2024
References:- WELIREG™M (belzutifan) tablets, for oral use. 12/2023. Merck Sharp & Dome LLC, Rahway, NJ, USA: 2023.