Abstract 1653P
Background
The multikinase inhibitor C was approved by the US FDA for RAIR DTC pts who progress after prior VEGFR-targeted therapy based on the COSMIC-311 study (NCT03690388), the only phase 3 study that included prior L-treated pts. At extended follow up (median 10.1 months) C maintained superior PFS vs P (HR 0.22) in the ITT population regardless of prior treatment (Capdevila, ESMO 2021: Abs LBA67). Here we show outcomes based on duration of prior L treatment.
Methods
Pts were randomized to C 60 mg QD or P. Primary endpoints were PFS (ITT population) and objective response rate (ORR; first 100 pts randomized), both per RECIST v1.1 by blinded independent review. P pts could cross over to open label C after confirmed progression of disease (PD). Outcomes were evaluated by duration of prior L treatment (>0–12, >12–24, >24 mo).
Results
At data cutoff (8 Feb 2021), 258 pts were randomized; 162 received prior L (C 107, P 55): 54 for >0–12 mo, 48 for >12–24, and 60 for >24. C was favored over P for PFS and response outcomes across prior L durations (Table). Discontinuation of C due to treatment-emergent AEs (TEAEs) occurred in 15% (>0–12), 25% (>12–24), and 12% (>24). Grade 3/4 TEAEs occurred in 52% for C vs 24% P in the >0–12 group; 72% vs 50% in >12–24; and 62% vs 28% in the >24 group. There were no grade 5 treatment-related AEs.
Conclusions
At extended follow-up of COSMIC-311, C maintained superior PFS vs P in DTC pts irrespective of prior L treatment duration. AEs were consistent with the overall population. Table: 1653P
| Prior L >0–12 mo | Prior L >12–24 mo | Prior L >24 mo | ||||
| C N=33 | P N=21 | C N=32 | P N=16 | C N=42 | P N=18 | |
| Median PFS (95% CI), mo | 5.6 (3.8–NE) | 1.9 (1.6–5.1) | 9.2 (4.3–NE) | 3.6 (1.7–3.9) | 5.8 (4.4–9.3) | 1.9 (1.1–3.5) |
| HR 95% CI | 0.32 (0.15–0.69) | 0.22 (0.10–0.51) | 0.28 (0.14–0.55) | |||
| ORR (95% CI), % | 12 (3.4–28.2) | 0 (0–16.1) | 0 (0–10.9) | 0 (0–20.6) | 5 (0.6–16.2) | 0 (0–18.5) |
| Best overall response, n (%)* | ||||||
| Complete | 0 | 0 | 0 | 0 | 1 (2) | 0 |
| Partial | 4 (12) | 0 | 0 | 0 | 1 (2) | 0 |
| Stable disease | 18 (55) | 6 (29) | 25 (78) | 8 (50) | 32 (76) | 5 (28) |
| PD | 3 (9) | 13 (62) | 5 (16) | 6 (38) | 2 (5) | 9 (50) |
| Not evaluable | 1 (3) | 0 | 0 | 1 (6) | 2 (5) | 0 |
| Missing | 6 (18) | 2 (10) | 2 (6) | 1 (6) | 4 (10) | 4 (22) |
*1 C-treated pt in the >0–12 subgroup had no disease.
Clinical trial identification
NCT03690388.
Editorial acknowledgement
Suvajit Sen, PhD; Exelixis, Inc.
Legal entity responsible for the study
Exelixis, Inc.
Funding
Exelixis, Inc.
Disclosure
M.S. Brose: Financial Interests, Personal, Other, Honoraria: Bayer, Eisai, Lilly; Financial Interests, Personal, Advisory Role: Bayer, Blueprint Medicines, Eisai, Exelixis, Lilly, Loxo; Financial Interests, Institutional, Research Grant: Bayer, Blueprint Medicines , Eisai, Exelixis, Lilly, Loxo . J.A. Krajewska: Financial Interests, Personal, Advisory Role: Bayer Health Care, Exelixis, Loxo; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Bayer Health Care, Eisai, Exelixis, Ipsen, Lilly, Novartis, Sanofi-Genzyme. A.O. Hoff: Financial Interests, Personal, Expert Testimony, Or Advisory Role: Exelixis, Inc., Bayer, Eli-Lilly; Financial Interests, Personal, Other, Honoraria (< $5000/year): Bayer, Eli-Lilly, Exelixis, Inc.; Financial Interests, Institutional, Research Grant: Eli-Lilly, Exelixis, Inc., Roche, Novartis. J. Oliver: Financial Interests, Personal, Full or part-time Employment: Exelixis, Inc.; Financial Interests, Personal, Stocks/Shares: Exelixis, Inc. D.S. Williamson: Financial Interests, Personal, Full or part-time Employment: Exelixis, Inc.; Financial Interests, Personal, Stocks/Shares: Exelixis, Inc. N. Berry: Financial Interests, Personal, Full or part-time Employment: Exelixis, Inc.; Financial Interests, Personal, Stocks/Shares: Exelixis, Inc. J. Capdevila Castillon: Financial Interests, Personal, Invited Speaker: Novartis, Pfizer, Ipsen, Exelixis, Bayer, Eisai, Advanced Accelerator Applications, Amgen, Sanofi, Lilly, Merck Serono; Financial Interests, Personal, Advisory Board: Pfizer, Ipsen, Exelixis, Bayer, Eisai, Advanced Accelerator Applications, Amgen, Sanofi, Lilly, Merck Serono; Financial Interests, Personal, Research Grant: Novartis, Pfizer, AstraZeneca, Advanced Accelerator Applications, Eisai, Bayer. All other authors have declared no conflicts of interest.