(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. Martin Zarba presented the results of a real-world analysis from the International mRCC Database Consortium (IMDC) of systemic treatments in favorable and very favorable risk metastatic renal cell carcinoma (RCC).
Dr. Zarba noted that the role of immunotherapy combinations in metastatic RCC patients with IMDC favorable risk disease at baseline remains controversial, with an absence of an overall survival benefit in this subgroup of patients across all pivotal trials in this disease space (Checkmate 214, KEYNOTE 426, Checkmate 9ER, CLEAR, Javelin RENAL 101 and IMmotion 151). A ‘very favorable’ risk subgroup within the favorable group has been described, with such patients meeting the following criteria:
- Primary diagnosis to systemic therapy ≥3 years
- Absence of brain, liver, or bone metastases
- Karnofsky Performance Status of 90–100%
To date, there is no data regarding the efficacy of immunotherapy combinations in this risk subgroup. To this end, Dr. Zarba and colleagues used the IMDC database to select patients with favorable risk disease who initiated systemic therapy between 2016 and 2023 and identified those patients with ‘very favorable’ risk disease. They evaluated two-year overall survival, objective response rate, treatment duration, and time to next treatment, stratified by the 1st line treatment received. They evaluated unadjusted survival rates at two years and performed Cox regression modeling with VEGF inhibitors (VEGFi) as the control reference.
The baseline patient characteristics are summarized below. This analysis included a total of 611 patients with favorable risk disease, of whom 165 (27%) had very favorable risk. The median patient age was 65 years. Only 5% of patients had sarcomatoid features (1.5% in very favorable risk group). Almost all patients had undergone a prior radical nephrectomy. The lung was the most common site of metastatic disease (66%). 77.3% of patients (70.3% in very favorable) had >1 site of metastatic disease.
The most commonly administered class of agents in the 1st line setting was a VEGFi (57.7% in overall cohort; 55.8% in very favorable risk subgroup). Other agents given included combination ipilimumab + nivolumab (15%) and IO + VEGFi (27.4%).
At a median follow-up of 33 months, there were no significant differences in overall survival between favorable risk patients treated with VEGFi, ipilimumab + nivolumab, or IO + VEGFi (p=0.60). Similarly no survival differences were observed between the treatment groups in the very favorable risk subgroup (p=0.41).
The best overall response rates in the favorable risk group were observed with the IO + .i combination (51.4%). This was similarly corroborated in the very favorable risk subgroup (58.1%), although patients receiving VEGFi had a similar ORR (55%).
The longest treatment durations for both favorable and very favorable risk patients were observed for those treated with IO + VEGFi (22.4 and 32.1 months, respectively).
Dr. Zarba concluded as follows:
- In all favorable risk patients
- There was no significant difference in 2-year overall survival between the treatment regimens.
- However, the IO + VEGFi regimen demonstrated superior outcomes compared to VEGFi in terms of objective response rate, treatment duration, and time to next therapy,
- In the subgroup of patients with very favorable risk disease:
- There was a statistically significant worse 2-year OS (HR 3.19; p=0.041) and objective response rate (p=0.039) with IPI-NIVO compared to other regimens
- This suggests the importance of including a VEGF inhibitor in the treatment regime for this patient subset.
- Future directions:
- With a median follow-up of 33 months, ongoing updates are anticipated to further evaluate the long-term durability of these treatment outcomes.
- Additional prospective trials are essential to confirm these preliminary findings and guide treatment strategies.
Presented by: Martin Zarba, MD, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta
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