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
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 risk | 0 | 2 (12%) | 11 (18%) | 24 (36%) |
Intermediate-Poor IMDC risk | 28 (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) |
Disclaimer
This material on this page is ©2024 American Society of Clinical Oncology, all rights reserved. Licensing available upon request. For more information, please contact licensing@asco.org
Abstract Disclosures
2022 ASCO Annual Meeting
First Author: Kelly N. Fitzgerald
2022 ASCO Annual Meeting
First Author: Linda Wu
2022 ASCO Genitourinary Cancers Symposium
First Author: Hamid Emamekhoo
2024 ASCO Annual Meeting
First Author: Ahmad A. Tarhini