Michele Ghidini, MD, Ph.D., Medical Oncologist, Fondazione IRCCS Ca"™ Granda Ospedale Maggiore Policlinico Milan, Italy speaks about Body weight loss (BWL) as a prognostic/predictive factor in previously treated patients (pts) with metastatic gastric or gastroesophageal junction cancer (mGC/GEJC): Post-hoc analyses of the phase III tags trial
Context:
Nutritional status is closely related to cancer mortality, and in curative, first- and second-line settings in mGC/GEJC, BWL has been shown to be prognostic for survival. Trifluridine/tipiracil (FTD/TPI) demonstrated clinical advantage against placebo (PBO) and manageable protection in pts with mGC/GEJC that had obtained = 2 previous chemotherapy regimens in the phase III TAGS trial. Retrospective studies investigated the correlation of early BWL with survival results in TAGS.
Methodology:
The population of TAGS intent-to-treat (ITT) was classified into pts that encountered <3% or =3% BWL from the start of treatment to day 1 of cycle 2. (each cycle: 28 days). Because of significant early BWL imbalances between treatment arms, overall survival (OS) and progression-free survival (PFS) were compared among subgroups within each treatment arm. A univariate Cox proportional hazards (PH) model as well as a multivariate Cox PH model that adjusted for baseline prognostic factors found in the initial ITT analysis evaluated the impact of early BWL on OS.
Outcomes:
In the sample, 451 of 507 (89 percent) pts (n=304, FTD/TPI; n=147, PBO) were available for body weight data. 74% (224/304 pts) and 65% (95/147) experienced <3% BWL in the FTD/TPI and PBO arms, respectively, while 26% (80/304) and 35% (52/147) experienced =3% BWL at the end of cycle 1. In both the FTD/TPI (median [m] OS: 6.5 vs 4.9 months [mo]; danger ratio [HR], 0.75; 95 percent CI, 0.55-1.02) and PBO weapons (mOS: 6.0 vs 2.5 mo; HR, 0.32; 95 percent CI, 0.21-0.49), Pts with <3 percent BWL had longer OS than those with = 3 percent BWL. The PFS HR in the FTD/TPI group for pts with <3 percent BWL vs =3 percent BWL was 0.95 (95 percent CI, 0.71"“1.25; mPFS, 2.1 vs 1.9 mo) and 0.49 (95 percent CI, 0.34"“0.72; mPFS, 1.9 vs 1.7 mo) in the PBO group for pts with <3 percent BWL vs = 3 percent BWL. The unadjusted HR for the <3 percent vs =3 percent BWL category estimated using a univariate Cox model was 0.58 (95 percent CI, 0.46"“0.73) in the pooled ITT population, suggesting a strong early BWL prognostic effect. Multivariate analysis findings were consistent with univariate analysis and indicated that early BWL in pts with mGC/GEJC was both a prognostic (P<0.0001) and predictive (interaction P=0.0003) factor for OS. In 77 percent and 82 percent of FTD/TPI-treated pts in the <3 percent and =3 percent BWL subgroups, respectively, and in 45 percent and 67 percent of placebo-treated pts in the <3 percent and =3 percent BWL subgroups, Grade=3 adverse events (AEs) of any cause were registered.
Findings:
To our knowledge, this is the first research to show that BWL is negatively correlated with survival in pts with third- or later-line care obtained by mGC/GEJC. Early BWL (= 3 percent BWL at the end of cycle 1) in TAGS was a clear negative prognostic factor for OS independent of treatment with FTD/TPI or PBO. In FTD/TPI-treated pts with <3 percent or =3 percent BWL, grade = 3 AE frequencies were close. BWL’s relationship to other prognostic factors will be further discussed.