Abstract 673P
Background
N and C are two approved agents after a prior TKI in mRCC pts. However, the optimal sequence, CN or NC, is still unknown. The superiority of C over everolimus in pts with prior anti-PD-1 (HR 0.22) in the METEOR trial suggests a sensitizing role of N. We conducted the CABIR study to identify the optimal sequence between CN and NC after one prior TKI.
Methods
In this multicenter retrospective study, we collected data from pts receiving CN or NC, after 1st line TKI. A propensity score (PS) was calculated to handle bias selection, and sequence comparisons were carried out with a cox model on a matched sample 1:1. A weighted 1:2 matching and a cox model with PS as adjusting covariate were also performed as sensibility analysis. Primary endpoint was progression-free survival (PFS) from the start of 2nd line to progression in 3rd line (PFS2/3), secondary endpoint was overall survival from 2nd line (OS2).
Results
Among the 135 pts included, 38 (28%) and 97 (72%) received CN and NC, respectively. Overlap in PS allowed 1:1 matching of all CN pts, with pts’ characteristics being well balanced. For both PFS2/3 and OS2, NC was superior to CN (PFS2/3: HR = 0.58 [0.34-0.98], p=0.043; OS2: 0.66 [0.42-1.05], p=0.080). Considering PFS2 and PFS3 separately, the only significant difference was in PFS3 in favor of C over N (p=0.0012). This difference was solely driven by pts previously treated with 6 to 18 months of 1st line TKI. Interaction between sequence and 1st line duration was significant in the matched cohort. Table: 673P
| Results of cox model | ||||
| Population | Number of patients (CN vs NC) | Outcome | HR (95%CI) | P-value |
| All with PS as covariate | 135 (38 vs 97) | PFS2/3 | 0.62 [0.39-0.98] | 0.039 |
| OS2 | 0.64 [0.43-0.95] | 0.028 | ||
| Matched 1:1 | 76 (38 vs 38) | PFS2/3 | 0.58 [0.34-0.98] | 0.043 |
| OS2 | 0.66 [0.42-1.05] | 0.080 | ||
| Matched 1:2 | 152 (76 vs 76) | PFS2/3 | 0.63 [0.43-0.92] | 0.016 |
| OS2 | 0.65 [0.46-0.90] | 0.009 |
Conclusions
We report here in a matching-adjusted comparison a prolonged OS and PFS with NC sequence compared to CN in mRCC pts treated with 6 to 18 months of prior TKI. Cabozantinib efficacy after N in 3rd line seems to drive this NC superiority strengthening the hypothesis of a sensitizing role of anti-PD-1 on TKI efficacy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
ARTIC - Association pour la Recherche de Thérapeutiques Innovantes en Cancérologie.
Funding
Ipsen.
Disclosure
Y. Vano: Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Institutional, Funding, Funding support for CABIR study: Ipsen. G. Gravis: Financial Interests, Institutional, Advisory Board: Merck; Financial Interests, Institutional, Invited Speaker: Amgen; Financial Interests, Institutional, Invited Speaker: Astellas; Financial Interests, Institutional, Advisory Board: BMS; Financial Interests, Institutional, Advisory Board: Janssen; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Invited Speaker: Sanofi; Financial Interests, Institutional, Principal Investigator: BMS; Financial Interests, Institutional, Sponsor/Funding. Janssen; Non-Financial Interests, Institutional, Principal Investigator: BMS; Non-Financial Interests, Institutional, Principal Investigator: Ipsen; Non-Financial Interests, Institutional, Principal Investigator: Merck. S.M. Oudard: Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Roche Genentech; Financial Interests, Personal, Advisory Board: Sanofi. All other authors have declared no conflicts of interest.