Richard Adams

IntroductionAfter induction therapy, maintenance strategies in metastatic colorectal cancer (mCRC) remain uncertain. Treatment breaks and thus a chemotherapy-free interval (CFI) may be considered when tumour control is achieved as well as maintenance therapy. Identifying predictors of a short/intermediate/long CFI would be useful to guide therapeutic decisions.Materials and MethodsCFI-PREDICT is an individual patient data meta-analysis assessing predictive factors of short (<3 months), intermediate (3–6 months) or long (≥6–12 months) CFI after induction chemotherapy. Data from 6 international trials comparing observation with continued systemic therapy were pooled. A prognostic score was developed using significant variables.Results1,188 patients were analysed. Median CFI was 3.67 months, 34%/42.5%/23.5% had short/intermediate/long CFIs. Multivariable analysis showed that male sex, old age, left-sided primary tumour, prior resection of the primary, single metastatic site and no thrombocytosis were associated with long CFI. A longer CFI was associated with an improved OS.DiscussionCFI-PREDICT is the first meta-analysis assessing CFI after induction therapy in mCRC. A simple prognostic score and useful nomogram based on routinely available clinical parameters were developed to help oncologists and patients with responding or stable mCRC, in shared decision-making (break vs. maintenance strategy).

PURPOSE: Colorectal cancer (CRC) incidence and mortality have decreased since the 1970s, but the incidence in young adults (v 6.8 months; hazard ratio [HR], 0.66 [95% CI, 0.54 to 0.80]; P < .0001), which was similar to the findings in aoCRC population (9.4 v 7.3 months; HR, 0.73 [95% CI, 0.67 to 0.80]; P < .001; interaction P = .5415). However, epithelial growth factor receptor inhibitor (EGFRi) did not improve PFS in RAS wild-type (WT) patients with eoCRC who had left-sided primary tumors (8.3 v 8.9 months; HR, 1.20 [95% CI, 0.81 to 1.77]; P = .36), whereas EGFRi significantly improved PFS in the aoCRC population (9.9 v 8.5 months; HR, 0.74 [95% CI, 0.64 to 0.86]; P < .0001; interaction P = .083). CONCLUSION: Treatment-naïve patients with metastatic eoCRC appear to derive similar benefit from bevacizumab as patients with aoCRC. However, patients with eoCRC with left-sided RAS/RAF WT tumors did not appear to derive benefit from first-line EGFRi.

PURPOSE: Several lines of treatment can be used sequentially in patients with metastatic colorectal cancer. We investigated the evolution of patient/tumor characteristics and their prognostic impact across treatment lines to develop an overall prognostic score (OPS). PATIENTS AND METHODS: Individual patient data from 48 randomized trials were analyzed. The end point was overall survival (from random assignment to death). Missing data were imputed. The complete data set was then separated into construction (80%) and validation sets (20%). The Cox's model was used to define risk groups for survival using the OPS. The discrimination capability was assessed in each treatment-line via bootstrapping to obtain optimism-corrected calibration and discrimination C-indices. Internal validation was done in the validation set. RESULTS: A total of 37,560 patients (26,974 in first-line [1L], 7,693 in second-line [2L], and 2,893 in third-line [3L]) were analyzed. Some clinical, biological, and molecular characteristics of patients/tumors included in therapeutic trials evolve over the lines. Seven independent prognostic variables were retained in the final multivariate model common to all lines: Eastern Cooperative Oncology Group performance status, hemoglobin, platelet count, WBC/absolute neutrophil count ratio, lactate dehydrogenase, alkaline phosphatase, and the number of metastatic sites. The OPS was used to define four patient subgroups with significantly different prognoses in 1L, 2L, and 3L, separately, with adequate C-indices: 0.65, 0.66, and 0.69 in the construction set and 0.65, 0.66, and 0.68 in the validation set, respectively. The OPS was not predictive, with 3L drugs ( v placebo) or subsequent line (2L/1L or 3L/2L) extending survival in all prognostic groups. CONCLUSION: The same prognostic model using practical variables can be used before all treatment lines. The OPS could better stratify patients in future clinical trials and help to therapeutic decision in routine practice.