1899P - Comparative effectiveness of second-line (2L) treatment (Rx) with cabozantinib (cabo) in patients (pts) with metastatic clear cell renal cell carcinoma (mccRCC) after first-line (1L) Rx with ipilimumab + nivolumab (ipi+nivo) vs. PD-1/L1 inhibitor (PDI) + tyrosine kinase inhibitor (TKI)

Background

The preferred 1L Rx for pts with mccRCC is either ipi+nivo or PDi + TKI (NCCN Guidelines V4.2023). Cabo was approved based on Ph3 METEOR trial results from pts after prior mccRCC progression on 1-2 TKIs but not PDi Rx. In real world, cabo is the most used 2L therapy but its effectiveness after prior PDi based combination is unknown.

Methods

De-identified nationwide (US based) Flatiron Health EHR-derived database was used. Inclusion: diagnosis of mccRCC, 1L Rx with ipi+nivo or PDi+TKI (from 10/2017 to 7/2022) followed by 2L Rx with single-agent cabo. Exclusion: 1L Rx with cabo, pts with no documentation of 1L Rx 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 at the data providing institution. 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 baseline covariates: age, race, smoking status, practice type, insurance, year of 1L, IMDC risk factors (all six), 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, 237 pts met eligibility, and all received ipi+nivo or PDi+TKI followed by cabo. Results summarized in table.

Table: 1899P

Conclusions

Cabo retained similar effectiveness in 2L regardless of prior ipi+nivo or PDi+TKI. These results may aid with counseling of pts, prognostication, treatment decision in clinic and design of future clinical trials.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

B.L. Maughan: Financial Interests, Personal and Institutional, Advisory Board, B.L.M is a 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: B.L.M is a 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 (. 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. U. Swami: Financial Interests, Personal and Institutional, Advisory Board, 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: 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, currentl. All other authors have declared no conflicts of interest.