Abstract 38P
Background
Selpercatinib (SELP) and pralsetinib (PRAL) are approved for RET fusion-positive advanced NSCLC, based on the LIBRETTO-001 and ARROW trials. No randomized direct comparison of SELP and PRAL is available or ongoing.
Methods
MAIC was conducted between the NSCLC data from LIBRETTO-001 (June 2021 datacut) and ARROW (March 2022 datacut). LIBRETTO-001 results were weighted to match ARROW baseline characteristics. Objective response rate (ORR), progression-free and overall survival (PFS and OS) were compared for treatment-naive (TN) and platinum-pretreated (PP) cohorts using 95% confidence intervals for hazard ratios (HR) and odds ratios (OR). Safety was also compared.
Results
Weighted ORRs were similar for SELP and PRAL, as were PFS and OS in TN patients (table). In PP patients, PFS and OS were significantly longer for SELP. There were fewer grade ≥3 treatment-related adverse events (TRAE) and lower rates of treatment discontinuation due to TRAE in patients receiving SELP. The difference in % of Asian patients impacted weighted results.
Table: 38PComparative efficacy and safety for SELP and PRAL in RET fusion-positive NSCLC estimated by MAIC
| Study measure, (95% CI) | SELP | PRAL | OR/HR Comparison (SELP vs PRAL) | |||
|---|---|---|---|---|---|---|
| TN (Neff = 37) | PP (Neff = 193) | TN (n = 116) | PP (n = 141) | TN | PP | |
| ORR, % | 77.1 | 59.2 | 72.4 | 59.6 | 1.29 | 0.98 |
| (67.4, 90.1) | (53.5, 64.7) | (63.3, 80.3) | (51.0, 67.7) | (0.67,4.06) | (0.70,1.43) | |
| Median PFS, mo | 17.1 | 24.9 | 12.5 | 16.3 | 0.81 | 0.67 |
| (11.5, 22.0) | (19.3, NR) | (9.2, 16.5) | (10.8, 22.2) | (0.52, 1.26) | (0.50, 0.90)* | |
| Median OS, mo | 32.3 | NR | NR | 44.3 | 1.20 | 0.68 |
| (18.5, NR) | (30.3, NR) | (31.9, NR) | (25.0, NR) | (0.69, 2.09) | (0.48, 0.97)* | |
| SELP NSCLC Safety Population | PRAL NSCLC Safety Population | OR (95% CI) | ||||
| (Neff = 247) | (N = 281) | |||||
| Grade ≥3 TRAEs, % | 39.3 | 62.6 | 0.39 | |||
| (34.8, 43.9) | (56.7, 68.3) | (0.29,0.49)* | ||||
| Discontinuation due to TRAEs, % | 3.6 | 10.0 | 0.34 | |||
| (1.4, 5.4) | (6.7, 14.1) | (0.14,0.58)* |
Conclusions
The efficacy of SELP and PRAL was similar. SELP was associated with fewer grade ≥3 TRAE and treatment discontinuations due to TRAE. Inherent limitations of MAIC are acknowledged.
Clinical trial identification
LIBRETTO 001 NCT03157128 ARROW NCT03037385.
Editorial acknowledgement
Medical writing and editing assistance was provided by Sara Musetti Jenkins and Paul Hobson, respectively, of RTI Health Solutions.
Legal entity responsible for the study
Eli Lilly and Company.
Funding
Eli Lilly and Company.
Disclosure
M.J. Hochmair: Financial Interests, Personal, Invited Speaker: Eli Lilly and Company, Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Daiichi-Sankyo, MSD, Roche, and Takeda; Financial Interests, Personal, Advisory Board: Eli Lilly and Company, Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Daiichi-Sankyo, MSD, Roche, and Takeda. E. Nadal: Financial Interests, Personal, Research Grant: Roche, Pfizer, Merck Serono, BMS; Financial Interests, Personal, Other, Consulting fees: Roche, Bristol Myers Squibb, Merck Sharp Dohme, Merck-Serono, Sanofi, Pfizer, Eli Lilly, Amgen, Boehringer Ingelheim, AstraZeneca, Takeda, Sanofi, Janssen and Bayer; Financial Interests, Personal, Invited Speaker: Roche, Bristol Myers Squibb, Merck Sharp Dohme, Merck-Serono, Sanofi, Pfizer, Eli Lilly, Amgen, Boehringer Ingelheim, AstraZeneca, Takeda, Sanofi, Janssen and Bayer; Financial Interests, Personal, Other, Support for attending meetings: MSD, BMS, Roche; Financial Interests, Personal, Advisory Board: Roche, MSD. Y. D'yachkova: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company. T. Puri: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company. A. Vickers: Financial Interests, Institutional, Other, AV is a full-time employee of RTI Health Solutions, an independent non-profit research organization, which was retained by Eli Lilly and Company to conduct the research which is the subject of this manuscript. Their compensation is unconnected to the studies on which they work: Eli Lilly and Company. S. Wolowacz: Financial Interests, Institutional, Sponsor/Funding, SW is a full-time employee of RTI Health Solutions, an independent non-profit research organization, which was retained by Eli Lilly and Company to conduct the research which is the subject of this manuscript. Their compensation is unconnected to the studies on which they work: Eli Lilly and Company. X. Wang: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company. U. Kiiskinen: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company.