1898P - Comparative real-world effectiveness of PD-1/L1 inhibitor (PD-1i) plus cabozantinib (cabo) vs cabo after progression with prior immune checkpoint inhibitor (ICI) treatment (Rx) in metastatic clear cell renal cell carcinoma (mccRCC)

Background

ICI rechallenge in solid tumors (including in mccRCC) after discontinuation or disease progression following a prior ICI is often practiced in the clinic and is an area of active investigation. Two ph 3 trials (NCT04338269/Contact-3 and NCT04987203/TiNivo-2) are evaluating this Rx paradigm in mccRCC. Cabo is the most common 2L Rx in mccRCC.

Methods

This study used the de-identified nationwide (US based) Flatiron Health EHR-derived database. Inclusion: diagnosis of mccRCC, receipt of 1L Rx with any ICI based Rx (between 3/2016 to 7/2022) followed by receipt of 2L Rx with cabo or cabo + PD-1i (between 6/2018 to 9/2022). Exclusion: 1L Rx with cabo, or pts with no evidence of contact for 90 days from diagnosis of mccRCC at treating institution to ensure pts were actively engaged in care. TTNT (time to next therapy; measured from 2L to 3L) and overall survival (OS; measured from 2L) were summarized via Kaplan-Meier survival estimates with 95% confidence interval (CI) and compared in the context of propensity score (PS) matching weighted analysis and Cox proportional hazard model (PSM- CoxHzM). PS model included 1L baseline covariates: age, race, smoking status, practice type, insurance, year of 1L, six IMDC risk factors, and missingness of covariates. Missing data were multiply imputed using predictive mean matching on 50 chained equations. All analysis done using R version 4.2.3.

Results

Of 12,285 mccRCC pts in the dataset, 314 pts met eligibilty. Results summarized in table.

Table: 1898P

2L cabo vs cabo-PD-1i in pts with PD-1i based therapy in 1L

Conclusions

No benefit of adding PD-1i therapy to cabo vs cabo alone in 2 L was observed on PSM – CoxHzM. These results from a real world mccRCC pts are similar to those in a recent press-release on CONTACT-03 trial and question the practice of ICI rechallenge in mccRCC and other solid tumors.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

U. Swami: Financial Interests, Personal and Institutional, Advisory Board, a consulting or advisory role by Seattle Genetics, Astellas Pharma, Exelixis, Imvax, and AstraZeneca, currently or during the past 2 years. Dr. Swami’s institution has received research funding from Janssen, Seattle Genetics/Astellas, and Exelixis, currently or within the past 2 years: a consulting or advisory role by Seattle Genetics, Astellas Pharma, Exelixis, Imvax, and AstraZeneca, currently or during the past 2 years. Dr. Swami’s institution has received research funding from Janssen, Seattle Genetics/Astellas, and Exelixis, Curren. B.L. Maughan: Financial Interests, Personal and Institutional, Advisory Board, paid consultant/advisor to AbbVie, Pfizer, AVEO oncology, Janssen, Astellas, BMS, Clovis, Tempus, Merck, Exelixis, Bayer Oncology and Peloton Therapeutics; Huntsman Cancer Institute has received research funding from Exelixis (Inst), Bavarian-Nordic (Inst), Clovis (Inst), Genentech (Inst) and BMS (Inst) on his behalf: paid consultant/advisor to AbbVie, Pfizer, AVEO oncology, Janssen, Astellas, BMS, Clovis, Tempus, Merck, Exelixis, Bayer Oncology and Peloton Therapeutics; Huntsman Cancer Institute has received research funding from Exelixis (Inst), Bava. N. Agarwal: Financial Interests, Personal and Institutional, Advisory Board, Consultancy to Astellas, AstraZeneca, Aveo, Bayer, BMS, Calithera, Clovis, Eisai, Eli Lilly, EMD Serono, Exelixis, Foundation Medicine, Genentech, Gilead, Janssen, Merck, MEI Pharma, Nektar, Novartis, Pfizer, Pharmacyclics, and Seattle Genetics. Research funding to Neeraj Agarwal's institution: Arnivas, Astellas, AstraZeneca, Bavarian Nordic, Bayer, BMS, Calithera, Celldex, Clovis, Crispr, Eisai, Eli Lilly, EMD Serono, Exelixis, Genentech, Gilead, GSK, Immunomedics, Janssen, Lava, Medivation, Merck, Nektar, Neoleukin, New Link Genetics, Novartis, Oric, Pfizer, Prometheus, Rexahn, Roche, Sanofi, Seattle Genetics, Takeda, and Tracon: Consultancy to Astellas, AstraZeneca, Aveo, Bayer, BMS, Calithera, Clovis, Eisai, Eli Lilly, EMD Serono, Exelixis, Foundation Medicine, Genentech, Gilead, Janssen, Merck, MEI Pharma, Nektar, Novartis, Pfizer, Pharmacyclics, and Seattle G. All other authors have declared no conflicts of interest.