KEY TAKEAWAYS
- The phase 3 CanStem303C (NCT02753127) trial aimed to evaluate the efficacy of napabucasin when added to FOLFIRI compared to FOLFIRI alone in patients with metastatic colorectal cancer (mCRC), with a focus on OS.
- Adults with histologically confirmed mCRC that progressed on first-line fluoropyrimidine plus oxaliplatin ± bevacizumab were randomized to receive either napabucasin plus FOLFIRI or FOLFIRI alone.
- The study found that adding napabucasin to FOLFIRI did not improve OS in patients with previously treated mCRC.
Investigational Drug Napabucasin, a Reactive Oxygen Species Generator Activated by NAD(P)H: quinone oxidoreductase 1, Shows Potential in mCRC Treatment, With pSTAT3 as a Potential Biomarker. The Phase 3 CanStem303C Study Evaluated Napabucasin Plus FOLFIRI vs. FOLFIRI Alone in Previously Treated mCRC Patients, With OS as the Primary Endpoint, Stratified by pSTAT3 Status.
The study involved 624 patients who received napabucasin and 629 patients who received control treatment, the median overall survival (OS) was 14.3 months for the napabucasin group and 13.8 months for the control group, with a hazard ratio of 0.976 and a one-sided P-value of 0.74. Among all patients, 44% were biomarker-positive, with 275 patients in the napabucasin group and 272 patients in the control group. In the biomarker-positive group, the median OS was 13.2 months for napabucasin and 12.1 months for the control, with a hazard ratio (0.969; one-sided P > .99). The control group showed a shorter median OS for biomarker-positive patients compared to biomarker-negative patients (12.1 vs. 18.5 months) with a hazard ratio of 1.518 and a nominal two-sided P-value of 0.0002. The most common treatment-emergent adverse events were diarrhea (napabucasin, 84.6%; control, 53.9%), nausea (60.5%, 50.5%), vomiting (41.2%, 29.3%), and abdominal pain (41.0%, 25.2%). Grade ≥3 treatment-emergent adverse events occurred in 73.8% of napabucasin-treated patients and 66.7% of control-treated patients. The most common grade ≥3 treatment-emergent adverse events were diarrhea, decreased neutrophil count (13.7%, 19.2%), and neutropenia (13.3%, 15.2%). Safety profiles were similar in biomarker-positive patients.
Adding napabucasin to FOLFIRI did not improve OS in patients with previously treated mCRC. The results from the control group suggest that pSTAT3 is an unfavorable prognostic factor in mCRC.
Source: https://pubmed.ncbi.nlm.nih.gov/36503738/
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT02753127/
Shah MA, Yoshino T, Tebbutt NC, Grothey A, Tabernero J, Xu RH, Cervantes A, Oh SC, Yamaguchi K, Fakih M, Falcone A, Wu C, Chiu VK, Tomasek J, Bendell J, Fontaine M, Hitron M, Xu B, Taieb J, Van Cutsem E. Napabucasin Plus FOLFIRI in Patients With Previously Treated Metastatic Colorectal Cancer: Results From the Open-Label, Randomized Phase III CanStem303C Study. Clin Colorectal Cancer. 2023 Mar;22(1):100-110. doi 10.1016/j.clcc.2022.11.002. Epub 2022 Nov 11. PMID: 36503738.
