Abstract 10P
Background
TFS is an emerging clinical endpoint that measures the time between treatment (Tx) cessation and subsequent Tx initiation or death. This framework divides restricted mean (r-mean) overall survival (OS) into periods on and off Tx, with/without toxicity. In CM227, mNSCLC pts received 1L Tx with either NIVO+IPI up to a maximum of 2 years or PDC, up to four cycles with optional maintenance for non-squamous pts.
Methods
Data were analyzed for pts randomized to NIVO+IPI (n=583) or PDC (n=583) in CM227. OS was estimated by Kaplan-Meier (KM) method. TFS was defined as the area between KM curves for 2 time-to-event endpoints defined from randomization: time to protocol Tx cessation and time to subsequent Tx/death. TFS was also divided into TFS with/without ongoing grade (gr) ≥3 treatment-related adverse events (TRAEs). The area under the KM curves was estimated by the 4-year r-mean time and expressed as a percentage of this period.
Results
Over 4 years, pts’ r-mean OS was 23.27 and 19.06 months and r-mean time on protocol therapy was 8.31 and 5.6 months for NIVO+IPI and PDC, respectively (Table). Pts spent 18.1% vs 9.1% of the 4-year period in TFS with NIVO+IPI and PDC, respectively (r-mean TFS, 8.70 and 4.38 months). NIVO+IPI pts had r-mean TFS that was 4.32 months longer than PDC pts (95% CI, 2.47, 6.16). Mean TFS with gr ≥3 TRAEs was a small proportion of the 4- year period, 0.9%, and 0.3% with NIVO+IPI and PDC, respectively. Table: 10P
Estimated r-mean (months) OS and TFS over 4 years
| NIVO+IPI | PDC | Δ (95% CI) | |
| OS | 23.27 | 19.06 | 4.21 (2.22, 6.19) |
| Survival after subsequent Tx | 6.26 | 9.08 | -2.82(-5.40, -0.23) |
| TFS | 8.70 | 4.38 | 4.32 (2.47, 6.16) |
| w/o gr ≥3 TRAEs | 8.27 | 4.26 | 4.01 (2.15, 5.87) |
| w/ gr ≥3 TRAEs | 0.43 | 0.13 | 0.31 (-0.87, 1.49) |
| Time on protocol Tx | 8.31 | 5.60 | 2.71 (1.89, 3.53) |
| w/o gr ≥3 TRAEs | 8.02 | 5.41 | 2.61 (1.80, 3.53) |
| w/ gr ≥3 TRAEs | 0.30 | 0.20 | 0.09 (0.02, 0.17) |
Conclusions
In this CM227 analysis, NIVO+IPI conferred longer r-mean TFS with/without toxicity compared to PDC, doubling the proportion of the 4-year period in TFS. The majority of TFS time in both arms was spent without gr ≥3 TRAEs.
Clinical trial identification
NCT02477826.
Legal entity responsible for the study
Bristol Myers Squibb.
Funding
Bristol Myers Squibb.
Disclosure
S. Peters: Consultation / Advisory role: AbbVie, Amgen, AstraZeneca, Bayer, Beigene, Biocartis, Boehringer Ingelheim, Bristol Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, ecancer, Eli Lilly, Elsevier, Fishawack, Foundation Medicine, Illumina, Imedex, IQVIA, Incyte, Janssen, Medscape, Merck Sharp & Dohme, Merck Serono, Merrimack, Novartis, OncologyEducation, PharmaMar, Phosplatin Therapeutics, PER, Pfizer, PRIME, Regeneron, RMEI, Roche/Genentech, RTP, Sanofi, Seattle Genetics, Takeda, Talk in a company's organized public event: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, ecancer, Eli Lilly, Illumina, Imedex, Medscape, Merck Sharp & Dohme, Novartis, PER, Pfizer, Prime, Roche/Genentech, RTP, Sanofi, Takeda, Receipt of grants/research supports: (Sub)investigator in trials (institutional financial support for clinical trials) sponsored by Amgen, AstraZeneca, Biodesix, Boehringer Ingelheim, Bristol Myers Squibb, Clovis, GlaxoSmithKline, Illumina, Lilly, Merck Sharp & Dohme, Merck Serono, Mirati, Novartis, Pfizer, Phosplatin Therapeutics, Roche/Genentech. J. Penrod: Financial Interests, Institutional, Full or part-time Employment: Bristol Myers Squibb. J. Li, S. Lubinga, R. Gupta: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. J. Bushong: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. J. Rizzo: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb; Financial Interests, Personal, Other, Patent Filing: Bristol Myers Squibb. S. Ramalingam: Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: Genmab; Financial Interests, Institutional, Sponsor/Funding: Amgen; Financial Interests, Institutional, Sponsor/Funding: Advaxis; Financial Interests, Institutional, Sponsor/Funding: Pfizer; Financial Interests, Institutional, Sponsor/Funding: AstraZeneca; Financial Interests, Institutional, Sponsor/Funding: Bristol Myers Squibb; Financial Interests, Institutional, Sponsor/Funding: Merck; Financial Interests, Institutional, Sponsor/Funding: Takeda; Financial Interests, Institutional, Sponsor/Funding: Genmab.