Impact of sarcomatoid features on treatment outcomes in metastatic clear cell renal cell carcinoma treated with first-line immunotherapy combinations.

Authors

null

Kelly N. Fitzgerald

Memorial Sloan Kettering Cancer Center, New York, NY

Kelly N. Fitzgerald , Cihan Duzgol , Andrea Knezevic , Natalie Shapnik , Ritesh R Kotecha , David H Aggen , Maria Isabel Carlo , Neil J. Shah , Martin H Voss , Darren R. Feldman , Robert J. Motzer , Chung-Han Lee

Organizations

Memorial Sloan Kettering Cancer Center, New York, NY, Memorial Sloan Kettering Cancer Center and Weill Medical College, New York, NY

Research Funding

Other
Memorial Sloan Kettering Cancer Center Support Grant/Core Grant P30 CA008748

Background: The presence of sarcomatoid features in clear cell renal cell carcinoma (cRCC) has historically been associated with poor response to tyrosine kinase inhibitor (TKI) monotherapy and poor overall survival; however, immunotherapy (IO) combination therapies have shown more promise in treating this variant. Front-line anti-PD-1 based IO combinations used in ccRCC include ipilimumab/nivolumab (IO/IO) and several combinations of a VEGFR-targeted TKI with a PD-1 inhibitor (TKI/IO). Here, we compare progression-free survival after therapeutic 1st-line (PFS) and 2nd-line (PFS-2) in patients who received IO/IO vs TKI/IO combinations as 1st line treatment for metastatic ccRCC, and test whether the treatment effects differ based on the presence or absence of sarcomatoid dedifferentiation. Methods: A retrospective analysis was performed on patients with ccRCC initiating 1st line combination IO at Memorial Sloan Kettering Cancer Center between 1/1/2014 and 12/30/2020. Patient cohorts were defined by 1st line treatment type: IO/IO or TKI/IO. PFS and PFS-2 were estimated using the Kaplan-Meier method. Restricted mean survival time (RMST) was calculated for PFS and PFS-2 in each 1st line treatment group and modelled using a generalized linear model adjusted for IMDC risk. To test for heterogeneity of treatment effect among subgroups, sarcomatoid features (presence/absence) is included in the models and an interaction test is performed. Results: Ninety patients (28 sarcomatoid) received 1st line IO/IO and 83 (17 sarcomatoid) received 1st line TKI/IO. Median PFS time is 6.8 months (95% CI: 4.5, 12.2) for IO/IO and 21 months (95% CI: 15, 25) for TKI/IO, p=0.009. After adjusting for IMDC risk, and after 48 months of follow-up, RMST for PFS was 10 months for IO/IO and 24 months for TKI/IO (p=0.02) and RMST for PFS-2 was 20 months for IO/IO and 23 months for TKI/IO (p=0.24). In the RMST model, the interaction between treatment group and presence or absence of sarcomatoid features is not significant for PFS (0.95) or PFS-2 (0.29). Conclusions: For ccRCC patients treated with 1st line IO/IO or TKI/IO, adjusted RMST for PFS was significantly longer for the TKI/IO group, but there was no statistically significant difference in adjusted RMST for PFS-2. Anti-PD-1-based therapy is an effective approach to treating ccRCC with sarcomatoid features.

1st-line IO/IO, sarcomatoid (n=28)1st-line TKI/IO, sarcomatoid (n=17)1st-line IO/IO, non-sarcomatoid (n=62)1st-line TKI/IO, non-sarcomatoid (n=66)
Favorable IMDC risk02 (12%)11 (18%)24 (36%)
Intermediate-Poor IMDC risk28 (100%)15 (88%)51 (82%)42 (64%)
ORR1st (95% CI)39% (22, 59)94% (71, 100)37% (25, 50)58% (45, 70)
ORR2nd (95% CI)39% (17, 64)25% (3, 65)51% (35, 67)10% (3, 24)
Median PFS, months (95% CI)6 (3, 13)31 (7, NE)7 (4, 13)21 (14, 25)
Median PFS-2, months (95% CI)16 (12, NE)NE (15, NE)27 (19, NE)44 (26, NE)

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Abstract Details

Meeting

2023 ASCO Genitourinary Cancers Symposium

Session Type

Poster Session

Session Title

Poster Session C: Renal Cell Cancer; Adrenal, Penile, Urethral and Testicular Cancers

Track

Renal Cell Cancer,Adrenal Cancer,Penile Cancer,Testicular Cancer,Urethral Cancer

Sub Track

Therapeutics

Citation

J Clin Oncol 41, 2023 (suppl 6; abstr 687)

DOI

10.1200/JCO.2023.41.6_suppl.687

Abstract #

687

Poster Bd #

H19

Abstract Disclosures