TY - JOUR
T1 - Efficacy and safety of nivolumab plus ipilimumab in patients with metastatic variant histology (non-clear cell) renal cell carcinoma
AU - Moussa, Mohammad Jad
AU - Khandelwal, Jaanki
AU - Wilson, Nathaniel R.
AU - Malikayil, Kiran L.
AU - Surasi, Devaki Shilpa
AU - Bathala, Tharakeswara K.
AU - Lin, Yiyun
AU - Rao, Priya
AU - Tamboli, Pheroze
AU - Sircar, Kanishka
AU - Ajufo, Helen
AU - Elsayes, Khaled M.
AU - Shah, Amishi
AU - Johns, Andrew C.
AU - Goswami, Sangeeta
AU - Hasanov, Elshad
AU - Jonasch, Eric
AU - Msaouel, Pavlos
AU - Campbell, Matthew T.
AU - Alhalabi, Omar
AU - Tannir, Nizar M.
N1 - Publisher Copyright:
© Author(s) (or their employer(s)) 2025.
PY - 2025/2/12
Y1 - 2025/2/12
N2 - Background Nivolumab plus ipilimumab (nivo/ipi) is a standard of care first-line (1 L) therapy for patients with metastatic clear-cell renal cell carcinoma (ccRCC), but its role in patients with metastatic, non-ccRCC has not been fully defined. We report a single-institution experience with nivo/ipi in non-ccRCC. Methods Between November 2017 and February 2024, 55 patients with metastatic non-ccRCC received nivo/ipi at MD Anderson Cancer Center. The tumor response was assessed by blinded radiologists using RECIST v1.1. The overall response rate (ORR), progression-free survival (PFS), PFS milestone, duration of response (DoR), and overall survival (OS) were determined. Next-generation sequencing (NGS) was performed on available tumor specimens. Results Twenty-five (45.5%) patients had papillary histology (pRCC), 12 (21.8%) patients had chromophobe (chRCC), and 18 (32.7%) patients had unclassified RCC (uRCC). Fifty-two (94.5%) patients received nivo/ipi in 1 L. Sarcomatoid features (SF) were found in 20 (36.4%) cases. ORR was 48% (12/25) in pRCC, 25% (3/12) in chRCC (all 3 cases had SF), 27.8% (5/18) in uRCC, and 55% (11/20) across histologies with SF. The median PFS was 10.6 months (95% CI: 2.8 to 22.8) in pRCC, 3.6 months (95% CI: 0.9 - NE) in chRCC, and 3 months (95% CI: 2.1 to 7) in uRCC; 6-month milestone PFS was 56% (95% CI: 36.3 to 75.7), 41.7% (95% CI: 22 to 61.3), and 38.9% (95% CI: 21.7 to 56.1) in pRCC, chRCC, and uRCC, respectively. The median DoR for the entire cohort was 8.5 months (95% CI: 8 - NE). The median OS was 36.7 months (95% CI: 11.5 to 54.8) in pRCC, 25.7 months (95% CI: 0.9 - NE) in chRCC, and 11.1 months (95% CI: 6.5 - NE) in uRCC. Ten (18.2%) patients discontinued treatment due to treatment-related adverse events (AEs). Grade 3/4 immune-mediated AEs were noted in 17 (30.9%) patients. We performed NGS on 26 cases: TP53 (42%), PTEN (23%), and TERT (23%) alterations were most frequently found, with TERT and TP53 mutations enriched in pRCC and chRCC, respectively. Conclusion Nivo/ipi produced favorable outcomes in patients with pRCC supporting its use as 1 L therapy. Responses in patients with chRCC were noted exclusively with SF. Despite achieving an ORR of 27.8% with nivo/ipi, patients with uRCC had short PFS and inferior OS.
AB - Background Nivolumab plus ipilimumab (nivo/ipi) is a standard of care first-line (1 L) therapy for patients with metastatic clear-cell renal cell carcinoma (ccRCC), but its role in patients with metastatic, non-ccRCC has not been fully defined. We report a single-institution experience with nivo/ipi in non-ccRCC. Methods Between November 2017 and February 2024, 55 patients with metastatic non-ccRCC received nivo/ipi at MD Anderson Cancer Center. The tumor response was assessed by blinded radiologists using RECIST v1.1. The overall response rate (ORR), progression-free survival (PFS), PFS milestone, duration of response (DoR), and overall survival (OS) were determined. Next-generation sequencing (NGS) was performed on available tumor specimens. Results Twenty-five (45.5%) patients had papillary histology (pRCC), 12 (21.8%) patients had chromophobe (chRCC), and 18 (32.7%) patients had unclassified RCC (uRCC). Fifty-two (94.5%) patients received nivo/ipi in 1 L. Sarcomatoid features (SF) were found in 20 (36.4%) cases. ORR was 48% (12/25) in pRCC, 25% (3/12) in chRCC (all 3 cases had SF), 27.8% (5/18) in uRCC, and 55% (11/20) across histologies with SF. The median PFS was 10.6 months (95% CI: 2.8 to 22.8) in pRCC, 3.6 months (95% CI: 0.9 - NE) in chRCC, and 3 months (95% CI: 2.1 to 7) in uRCC; 6-month milestone PFS was 56% (95% CI: 36.3 to 75.7), 41.7% (95% CI: 22 to 61.3), and 38.9% (95% CI: 21.7 to 56.1) in pRCC, chRCC, and uRCC, respectively. The median DoR for the entire cohort was 8.5 months (95% CI: 8 - NE). The median OS was 36.7 months (95% CI: 11.5 to 54.8) in pRCC, 25.7 months (95% CI: 0.9 - NE) in chRCC, and 11.1 months (95% CI: 6.5 - NE) in uRCC. Ten (18.2%) patients discontinued treatment due to treatment-related adverse events (AEs). Grade 3/4 immune-mediated AEs were noted in 17 (30.9%) patients. We performed NGS on 26 cases: TP53 (42%), PTEN (23%), and TERT (23%) alterations were most frequently found, with TERT and TP53 mutations enriched in pRCC and chRCC, respectively. Conclusion Nivo/ipi produced favorable outcomes in patients with pRCC supporting its use as 1 L therapy. Responses in patients with chRCC were noted exclusively with SF. Despite achieving an ORR of 27.8% with nivo/ipi, patients with uRCC had short PFS and inferior OS.
KW - Genitourinary Cancer
KW - Immune Checkpoint Inhibitor
KW - Immunotherapy
KW - Kidney Cancer
KW - Solid tumor
UR - https://www.scopus.com/pages/publications/85217670328
U2 - 10.1136/jitc-2024-010958
DO - 10.1136/jitc-2024-010958
M3 - Article
C2 - 39939142
AN - SCOPUS:85217670328
SN - 2051-1426
VL - 13
JO - Journal for ImmunoTherapy of Cancer
JF - Journal for ImmunoTherapy of Cancer
IS - 2
M1 - e010958
ER -