SOLSTICE (colorectal cancer)
Trial question
Is first-line trifluridine-tipiracil plus bevacizumab superior to capecitabine plus bevacizumab in patients with metastatic CRC ineligible for intensive therapy?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
46.0% female
54.0% male
N = 856
856 patients (394 female, 462 male).
Inclusion criteria: adult patients with histologically confirmed metastatic CRC, ineligible for full-dose doublet or triplet chemotherapy and curative resection.
Key exclusion criteria: pregnancy; symptomatic CNS metastases; major surgery within 4 weeks prior to randomization; allergy/contraindication to study drugs.
Interventions
N=426 trifluridine-tipiracil plus bevacizumab (oral trifluridine-tipiracil 35 mg/m² BID on days 1-5 and 8-12 plus 5 mg/kg bevacizumab IV on days 1 and 15 of each 28-day cycle).
N=430 capecitabine plus bevacizumab (oral capecitabine 1,250 mg/m² BID on days 1-15 of each cycle plus 7.5 mg/kg intravenous bevacizumab on day 1 of each 21-day cycle).
Primary outcome
Progression-free survival
9.4 months
9.3 months
9.4 months
7.1 months
4.7 months
2.4 months
0.0 months
Trifluridine-tipiracil plus
bevacizumab
Capecitabine plus
bevacizumab
No significant
difference ↔
No significant difference in progression-free survival (9.4 months vs. 9.3 months; HR 0.87, 95% CI 0.75 to 1.02).
Secondary outcomes
No significant difference in overall response rate (36% vs. 42%; RR 0.86, 95% CI -0.14 to 1.86).
No significant difference in disease control rates (86% vs. 85%; RR 1.01, 95% CI -2.9 to 4.92).
Safety outcomes
No significant difference in treatment-related deaths.
Significant differences in ≥ grade 3 treatment-emergent adverse events (52% vs. 1%), decreased neutrophil count (18% vs. < 1%), anemia (14% vs. 4%), hand-foot syndrome (0% vs. 15%).
Conclusion
In adult patients with histologically confirmed metastatic CRC, ineligible for full-dose doublet or triplet chemotherapy and curative resection, trifluridine-tipiracil plus bevacizumab was not superior to capecitabine plus bevacizumab with respect to a progression-free survival.
Reference
Thierry André, Alfredo Falcone, Yaroslav Shparyk et al. Trifluridine-tipiracil plus bevacizumab versus capecitabine plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer ineligible for intensive therapy (SOLSTICE): a randomised, open-label phase 3 study. Lancet Gastroenterol Hepatol. 2023 Feb;8(2):133-144.
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