Trajectories of body weight change and survival among patients with mCRC treated with systemic therapy: Pooled analysis from the ARCAD database

Background Higher body mass index is associated with a higher incidence of colorectal cancer (CRC) but also with improved survival in metastatic CRC (mCRC). Whether weight change after mCRC diagnosis is associated with survival remains largely unknown. Methods We analysed individual patient data for previously untreated patients enrolled in five phase 3 randomised trials conducted between 1998 and 2006. Weight measurements were prospectively collected at baseline and up to 59.4 months after diagnosis. We used stratified multivariable Cox models to assess the prognostic associations of weight loss with overall and progression-free survival, adjusting for other factors. The primary end-point was a difference in overall survival (OS) between populations with weight loss and stable or increasing weight. Findings Data were available for 3504 patients. The median weight change at 3 months was −0.54% (IQR −3.9 … +1.5%). We identified a linear trend of increasing risk of death associated with progressive weight loss. Unstratified median OS was 20.5, 18.0, and 11.9 months (p < 0.001) for stable weight or gain, <5% weight loss, and ≥5% weight loss at 3 months, respectively. Weight loss was associated with a higher risk of death (<5% loss: aHR 1.18 [1.06–1.30], p < 0.002; ≥5% loss: aHR 1.87 [1.67–2.1], p < 0.001) as compared to stable or increasing weight at 3 months post-baseline (reference), while adjusting for age, sex, performance, and a number of metastatic sites. Interpretation Patients losing weight during systemic therapy for metastatic colorectal cancer have significantly shorter OS. The degree of weight loss is proportional to the observed increased risk of death and remains evident among underweight, normal weight, and obese individuals. On-treatment weight change could be used as an intermediate end-point

BRAF V600E mutation in first-line metastatic colorectal cancer: an analysis of individual patient data from the ARCAD database

Background First-line therapeutic strategies for patients with BRAFV600E-mutated (BRAFmt) metastatic colorectal cancer (mCRC) mainly rely on subgroup analyses from randomized controlled trials (RCTs). We aimed at assessing the prognostic and predictive impact of BRAFmt for the efficacy of targeted therapies with first-line chemotherapy. Methods Individual patient data from first-line RCTs with BRAF and KRAS status data in the ARCAD database were pooled. Progression-free survival and overall survival (OS) were assessed using Kaplan-Meier and Cox models. Outcomes were compared between treatment groups that were concurrently randomized whenever possible. Results 6391 patients from 10 RCTs were included: 573 BRAFmt (9.0%), 2059 KRASmt (32.2%) and 3759 double wild-type (58.8%). BRAFmt mCRC patients experienced statistically significantly poorer OS than those with KRASmt (adjusted hazard ratio [HRadj] =1.46, 95% confidence interval [95%CI] = 1.30-1.64) and patients with double wild-type tumors (HRadj =2.14, 95%CI = 1.94-2.36). Anti-EGFR agents did not improve progression-free survival or OS of BRAFmt mCRC patients, based on 4 RCTs testing chemotherapy ± anti-EGFR (HRadj =0.96, 95%CI = 0.71-1.30 and HRadj =0.85, 95%CI = 0.66-1.14, respectively). Conclusion Our data suggest that the addition of anti-EGFR agents to chemotherapy is ineffective as first-line treatment for BRAFmt mCRC patients