(UroToday.com) The 2023 American Society of Clinical Oncology Genitourinary (ASCO GU) cancers symposium held in San Francisco, CA between February 16th and 18th was host to a Renal Cell Cancer; Adrenal, Penile, Urethral and Testicular Cancers poster session. Dr. Yann-Alexandre Vano presented the overall survival and second-line treatment efficacy in metastatic clear cell renal cell carcinoma patients treated in the randomized phase II BIONIKK trial.
Immune checkpoint inhibitor (CPI) combinations, including nivolumab + ipilimumab, have improved overall survival in patients with metastatic clear cell RCC. However, these combinations are associated with clinically significant immune-related toxicities, and there is no clear biomarker of efficacy to select the best combination for each patient.
In the BIONIKK trial,2 the authors recently reported that molecular subtyping of renal tumors into 4 groups (ccRCC 1 to 4) could help predict a higher objective response rate (ORR), prolonged progression-free survival (PFS) and time to subsequent treatment (TST) with nivo alone, nivo-ipi, and a VEGFR-TKI alone. The main findings were as follows:
- High efficacy of TKIs as well as nivo-ipi in ccRCC2 tumors
- Higher efficacy of nivo with or without ipi in ccRCC4 tumors compared to ccRCC1.
The main objectives of this current analysis are:
- To report for the first time the results of overall survival (OS), a key secondary endpoint of the BIONIKK phase 2 trial
- To report an exploratory post-hoc analysis of the efficacy of the 2nd line treatment received according to 1st line and tumor molecular group
BIONIKK is a French, multicenter randomized non-comparative trial including untreated mRCC patients according to their tumor molecular subgroup defined on a frozen tumor sample. Patients with ccRCC1 and ccRCC4 tumors were randomized to receive nivo alone or nivo/ipi, whereas patients with ccRCC2 and ccRCC3 tumors were randomized to receive nivo/ipi or a TKI alone. The primary endpoint was ORR, and the key secondary endpoints were PFS and OS. Initial results were published with a median follow up of 18 months. An amendment was obtained to continue to follow the efficacy of treatment in all patients until death.
In this trial, 199 patients were randomized to:
- Nivolumab: 58
- Nivol/Ipi: 101
- TKI: 40
After a median follow-up of 46.5 months (IQR: 41 – 54), 86 (43%) patients had died: 27/58 (46.5%), 39/101 (39%), and 20/40 (50%) in the nivolumab, nivo/ipi, and TKI arms, respectively, including 8, 9, and 5 patients during 1st line therapy, respectively.
With regards to baseline characteristics, 74% were male, 73% were ECOG PS 0, 72% had a prior nephrectomy, 30% were IMDC good risk and 70% IMDC intermediate/poor risk. Molecular group distribution is demonstrated in the table below.
The median overall survival outcomes were as follows:
- Nivo/Ipi: Not reached (IQR: 30 – not reached)
- Nivolumab: 35 months (IQR: 16 – not reached; HR compared to nivo/ipi: 1.56, 95% CI: 0.99 to 2.46)
- TKI: 45 months (IQR: 14 – not reached; HR compared to nivo/ipi: 1.29, 95% CI: 0.76 to 2.19)
Overall survival data by molecular group are demonstrated in the figure below. When evaluating the ccRCC1 and ccRCC4 cohorts, the benefit of combination nivo/ipi was most pronounced in the ccRCC4 subgroup, with patients receiving nivolumab alone having a 64% increased hazard of overall mortality (HR: 1.64 in favor of combination, 95% CI: 0.59 to 4.54).
Notably in the ccRCC3 subgroup, use of VEGFR-TKI, as opposed to nivo/ipi, was associated with a 3.2-fold increase in the OS hazard (HR: 3.2, 95% CI: 0.57 – 17.93).
An ORR was achieved in:
- Nivo: 20/58 (34.5%)
- Nivo/ipi: 49/101 (48.5%)
- TKI: 21/40 (52.5%)
ORR, median PFS, and TST according to molecular groups were consistent with those previously reported:
With regards to 2nd line treatment, 133 (67%) patient received a 2nd line treatment:
- Nivo: 40/58 (69%)
- Nivo/Ipi: 64/101 (64%)
- TKI: 29/40 (72.5%)
80% of patients received a TKI in the 2nd line setting:
- Nivo: 37/58 (64%)
- Nivo/Ipi: 52/64 (97%)
- TKI: 7/29 (24%)
- 20/40 (50%) of patients received nivolumab in 2nd line after TKI
With regards to the efficacy of TKI in the 2nd line setting, the median follow-up for patients receiving a TKI in the 2nd line was 34 months. An ORR in this setting was achieved in:
- Nivo: 27%
- Nivo/IPI: 45% (1 CR)
- TKI: 57% (1CR)
Cabozantinib was the most frequent TKI received in the 2nd line setting, 57/106 patients (54%), with comparable efficacy compared to the overall TKI-L2 cohort. Of note, for the 20 patients receiving nivo after TKI, ORR was 10%, mPFS was 3.3 (2.5 – 17) months, and median OS was 13.3 (7.7 – NE) months.
Median PFS2, defined as the time from onset of L1 to progression to L2 or death, was:
- Nivo-L1: 28 months (10-52)
- Nivo/Ipi-L1: 41 months (18 – NE)
- TKI-L1: 27 months (8 – NA)
When considering only patients who received a TKI in L2, median PFS2 was:
- Nivo-L1: 23 months (16-41)
- Nivo/Ipi-L1: 27 months (22-41)
- TKI-L1: 40 months (38-NE)
Presented by: Yann-Alexandre Vano, MD, Medical Oncologist at Georges Pompidou European Hospital, Paris, France
Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2023 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, Thurs, Feb 16 – Sat, Feb 18, 2023.
References:
- Powles T, et al. ESMO guidelines updated nov. 2021
- Vano Y, et al. Nivolumab, nivolumab–ipilimumab, and VEGFR-tyrosine kinase inhibitors as first-line treatment for metastatic clear-cell renal cell carcinoma (BIONIKK): a biomarker-driven, open-label, non-comparative, randomised, phase 2 trial. Lancet Oncology. 2022;23(5),612-624
Related Content:
Overall Survival and Efficacy Results of Second-line Treatment for Patients With Metastatic Clear Cell Renal Cell Carcinoma, BIONIKK Trial -Yann Vano