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The effect of duration of induction therapy on survival in patients receiving maintenance therapy in the first line for metastatic colorectal cancer: A single-center retrospective analysis
Background
Standard first-line treatment of metastatic colorectal cancer (mCRC) is combination chemotherapy with the addition of a biological agent. Several randomized clinical trials have investigated different strategies of continuing chemotherapy until progression compared with a period of either treatment break or the use of various maintenance therapies.
Methods
In this retrospective, observational, single-center study conducted in the University Hospital Centre Zagreb in Zagreb, Croatia, data were retrieved from medical records on 95 patients (59% men, 41% women) who began first-line treatment for mCRC between Jan 1, 2016 and Dec 31, 2018. The therapy regimen was chosen by the attending physician and depended on the patient's overall health, RAS/BRAF status and preferences. The duration of induction chemotherapy in patients who have responded depended on the attending physician choice and the patient’s preferences. Maintenance therapy consisted of fluoropyrimidine +/- bevacizumab, and patients who received anti-EGFR were deescalated to mono fluoropyrimidines. The objectives of this study were to compare the effectiveness in terms of overall survival (OS) and progression-free survival (PFS) with regard to the duration of the induction treatment period in the real-world setting. The follow-up was set at 36 months. Survival (OS and PFS) was estimated using the Kaplan-Meier method and curves of the different treatment groups were compared using the log-rank test. Cox regression analysis was used to examine the association between survival and other influencing factors (age, ECOG performance status, RAS/BRAF status, location of the primary tumor, local ablative treatment including surgical resection of metastases). Results were expressed as hazard ratios (HR) with 95% confidence interval (CI) with statistical significance set at a confidence level of P < 0.05.
Results
Patients were divided into two groups based on the duration of the induction therapy. There were 51 patients (54%) in group A with short induction period (≤6 months) and 44 patients (46%) in group B with long induction period (>6 months). Median age was 65 years. Patients in group B had significantly longer PFS than in group A, 25.8 vs. 18.7 months (p=0.005), respectively. However, there was no difference in OS between these two groups of patients, although there was a numerical trend in favor of group B (50.0 vs 35.8 months, p=0.056). Cox regression analysis showed longer OS in patients with RAS/BRAF wild type tumours (HR 0.49, 95% CI 0.24-1.02, p=0.005) and in those who underwent local ablative treatments (HR 0.52, 95% CI 0.33-0.89, p=0.017). Significantly more patients in group B had RAS/BRAF wild type tumours, compared to the group A (52.3 % vs. 27.5 %, p=0.019).
Conclusions
With all the limitations due to the retrospective nature of the study, our results suggest that patients could benefit from a longer induction period in terms of survival. However, this may be influenced by the different treatment approach between RAS mt and wt tumours. Considering patients heterogeneity and multiple factors that might influence OS further trials and real-world data are needed.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosures
All authors have declared no conflicts of interest.
