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A randomized, open-label, two-arm phase II trial comparing the efficacy of sequential ipilimumab (ipi) versus best supportive care (BSC) following first-line (1L) chemotherapy in patients with unresectable, locally advanced/metastatic (A/M) gastric or gastro-esophageal junction (G/GEJ) cancer.
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2016
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Advanced Gastric CancerCancer ManagementImmunologyGastroenterologySurgeryPharmacotherapyImmunotherapeuticsImmunotherapyGastrointestinal OncologySequential IpilimumabClinical TrialsTumor ImmunityRadiation OncologyMolecular OncologyCancer ResearchMonoclonal AntibodyHealth SciencesMedicineImmune SurveillanceCancer TreatmentTumor MicroenvironmentImmune Checkpoint InhibitorGastro-esophageal JunctionPoor PrognosisOncology
4011 Background: Pts with advanced gastric cancer have a poor prognosis with median overall survival (OS) of ~1 yr. Ipi is a monoclonal antibody that enhances T-cell activation and T-effector cell tumor infiltration and activity by inhibiting CTLA-4 receptor interaction with its ligands. This study (NCT01585987) evaluated efficacy of ipi vs BSC as sequential/maintenance therapy in pts with unresectable locally A/M G/GEJ cancer following 1L chemotherapy with platinum plus fluoropyrimidine. Methods: Eligible pts ≥18 years without progressive disease (PD) following 1L chemotherapy were randomized to ipi 10 mg/kg Q3W for 4 doses then ipi 10 mg/kg Q12W for up to 3 yrs, or BSC. Primary endpoint was immune-related progression-free survival (irPFS); secondary endpoints were PFS by modified WHO criteria (mWHO) and OS. Post-interim analysis (IA), the study was stopped. Updated OS are presented. Results: Of 143 pts screened, 57 were randomized to each arm. At the IA, improvement in irPFS with ipi vs BSC was not observed (HR=1.44 [80% CI: 1.09, 1.91], p=0.097). Treatment-related adverse events (AEs) occurred in 41/57 (72%) of ipi pts and 25/45 (56%) pts on active BSC. The most frequent ipi-related AEs of any grade were pruritus (32%), diarrhea (25%), fatigue (23%), and rash (18%), with no gastrointestinal perforations in the ipi arm. Conclusions: The irPFS was similar and median OS for both arms was approximately 1 yr. AEs were consistent with other ipi studies. These results suggest ipi in combination with chemotherapy warrants further study in pts with A/M G/GEJ cancer. Clinical trial information: NCT01585987.Survival. Ipi (n=57) BSC (n=57) p-value HR (80% CI) irPFSa Events, n (%) 51 (90) 40 (70) 0.097 1.44 (1.09–1.91) Median (mos) 95% CI 2.9 1.6–5.2 4.9 3.5–6.5 PFS by mWHOa Events, n (%) 52 (91) 40 (70) 0.034 1.59 (1.20–2.10) Median (mos) 95% CI 2.7 1.4–3.0 4.9 3.5–6.1 OSa Events, n (%) 25 (44) 25 (44) 0.643 0.87 (0.60–1.27) Median (mos) 95% CI 16.8 11.8–23.1 12.1 9.3–NE OSb Events, n (%) 36 (63) 30 (53) Median (mos) 95% CI 12.7 10.5–18.9 12.1 9.3–NE aat IA bat study end; NE, not estimable.