BackgroundIn the phase III RECOURSE trial, trifluridine/tipiracil (TAS-102) extended overall survival (OS) and progression-free survival (PFS) with an acceptable toxicity profile in patients with metastatic colorectal cancer refractory or intolerant to standard therapies. The present analysis investigated the efficacy and safety of trifluridine/tipiracil in RECOURSE subgroups.MethodsPrimary and key secondary end-points were evaluated using a Cox proportional hazards model in prespecified subgroups, including geographical subregion (United States of America [USA], European Union [EU], Japan), age (<65 years, ≥65 years) and v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homologue (KRAS) status (wild type, mutant). Safety and tolerability were reported with descriptive statistics.ResultsEight-hundred patients were enrolled: USA, n = 99; EU, n = 403; Japan, n = 266. Patients aged ≥65 years and those with mutant KRAS tumours comprised 44% and 51% of all patients in the subregions, respectively. Final OS analysis (including 89% of events, compared with 72% in the initial analysis) confirmed the survival benefit associated with trifluridine/tipiracil, with a hazard ratio (HR) of 0.69 (95% confidence interval [CI] 0.59–0.81; P = 0.0001). Median OS in the three regions was 6.5–7.8 months in the trifluridine/tipiracil arm and 4.3–6.7 months in the placebo arm (USA: HR 0.56; 95% CI 0.34–0.94; P = 0.0277; EU: HR 0.62; 95% CI 0.48–0.80; P = 0.0002; Japan: HR 0.75; 95% CI 0.57–1.00; P = 0.0470). Median PFS was 2.0–2.8 months for trifluridine/tipiracil and 1.7–1.8 months for placebo; HRs favoured trifluridine/tipiracil in all regions. Similar clinical benefits of trifluridine/tipiracil were observed in elderly patients and in those with mutant KRAS tumours. There were no marked differences among subregions in terms of safety and tolerability.ConclusionsTrifluridine/tipiracil was effective in all subgroups, regardless of age, geographical origin or KRAS status.This trial is registered with ClinicalTrials.gov: NCT01607957.
Non-V600E BRAF mutated colorectal cancer (CRC) is a rare disease entity with specific clinical features. These tumors are less likely to have microsatellite instability than CRC with a V600E BRAF mutation and often harbor a KRAS or NRAS mutation. Notably, median overall survival is longer than in wild-type BRAF CRC. Little is known about treatment possibilities in these patients. We present the case of a 59 year old patient with a rare mutation in BRAF codon 594, who progressed rapidly on all classical therapies but experienced a clear and long lasting response on treatment with Regorafenib. Little is known about therapies that can be effective in the rare non-V600E BRAF mutated CRCs. We present a patient who had a definite response to treatment with Regorafenib. There are no predictive markers that define a subset of CRC patients who benefit most from Regorafenib. The specific features of this non-V600E BRAF mutated CRC may be relevant in the exploration of predictive biomarkers for the efficacy of Regorafenib.
Introduction : Neoadjuvant multimodality treatment confers a survival benefit in locally advanced oesophageal cancer patients. The optimal dose of radiotherapy (RT) remains undefined.
Aim : To analyse the effect of RT dose on surgical outcome and survival in patients treated with multimodality treatment followed by surgery in locally advanced oesophageal cancer.
Methods : This was a retrospective comparative study based on a prospectively collected database. Patients with clinical stage III oesophageal cancer were treated with a combination of RT, cisplatin 80 mg/m2, and 5-FU 800 mg/m2. Radiation dose was 36 Gy (group 1) or 45-50 Gy (group 2), depending on the referring physician. Ivor Lewis oesophagectomy was performed after a 6-8 weeks period. Surgical and pathological outcome was compared using Fisher exact test. Overall survival (OS) and disease free survival (DFS) were calculated using the Kaplan Meier method, and the effect of RT dose on survival was tested using univariate (log rank test) analysis.
Results : A total of 134 patients were evaluated : 108 received 36 Gy, and 26 received 45-50 Gy. Mean age at surgery was 61 ± 9.43 years, and 84% were male. Median length of postoperative hospital stay was 17 days. Overall postoperative 30 day or in hospital mortality was 7.5%, and anastomotic leakage occurred in 4.1% ; neither was influenced by RT dose. Pathological complete response (pCR) was observed in 15.5% (group 1) and 31% (group 2), P = 0.09. No differences were observed in downstaging of either the T stage or the N stage. Overall five year OS and DFS were 35.1% and 38.3% respectively. In univariate analysis, a higher RT dose was associated with a significantly better DFS (P = 0.01), but not OS (P = 0.6).
Conclusion : In patients with locally advanced oesophageal cancer treated with neoadjuvant chemoradiation, a higher RT dose does not affect surgical outcome, enhances pCR rate and improves DFS without affecting OS.
