Abstract
BackgroundFew data regarding post-induction management following first-line anti-epidermal growth factor receptor (EGFR)-based doublet regimens in patients with left-sided RAS/BRAF wild-type metastatic colorectal cancer (mCRC) are available.MethodsThis multicenter, retrospective study aimed at evaluating clinicians’ attitude, and the safety and effectiveness of post-induction strategies in consecutive patients affected by left-sided RAS/BRAF wild-type mCRC treated with doublet chemotherapy plus anti-EGFR as first-line regimen, who did not experience disease progression within 6 months from induction initiation, at 21 Italian and 1 Spanish Institutions. The measured clinical outcomes were: progression-free survival (PFS), overall survival (OS), adverse events, and objective response rate (ORR).ResultsAt the data cutoff, among 686 consecutive patients with left-sided RAS/BRAF wild-type mCRC treated with doublet plus anti-EGFR as first-line regimen from March 2012 to October 2020, 355 eligible patients have been included in the present analysis. Among these, 118 (33.2%), 66 (18.6%), and 11 (3.1%) received a maintenance with 5-fluorouracil/leucovorin (5FU/LV)+anti-EGFR, anti-EGFR, and 5FU/LV, respectively, while 160 (45.1%) patients continued induction treatment (non-maintenance) until disease progression, unacceptable toxicity, patient decision, or completion of planned treatment. The median period of follow-up for the overall population was 33.7 months (95%CI = 28.9–35.6). The median PFS values of the 5FU/LV+anti-EGFR, anti-EGFR, 5FU/LV, and non-maintenance cohorts were 16.0 (95%CI = 14.3–17.7, 86 events), 13.0 (95%CI = 11.4–14.5, 56 events), 14.0 (95%CI = 8.1–20.0, 8 events), and 10.1 months (95%CI = 9.0–11.2, 136 events), respectively (p < 0.001). The median OS values were 39.6 (95%CI = 31.5–47.7, 43 events), 36.1 (95%CI = 31.6–40.7, 36 events), 39.5 (95%CI = 28.2–50.8, 4 events), and 25.1 months (95%CI = 22.6–27.6, 99 events), respectively (p < 0.001). After adjusting for key covariates, a statistically significant improvement in PFS in favor of 5FU/LV+anti-EGFR (HR = 0.59, 95%CI = 0.44–0.77, p < 0.001) and anti-EGFR (HR = 0.71, 95%CI = 0.51–0.98, p = 0.039) compared to the non-maintenance cohort was found. Compared to the non-maintenance cohort, OS was improved by 5FU/LV+anti-EGFR (HR = 0.55, 95%CI = 0.38–0.81, p = 0.002) and, with marginal significance, by anti-EGFR (HR = 0.67, 95%CI = 0.51–0.98, p = 0.051). No difference was found in ORR. Any grade non-hematological and hematological events were generally higher in the non-maintenance compared to the maintenance cohorts.ConclusionAmong the treatment strategies following an anti-EGFR-based doublet first-line induction regimen in patients affected by left-sided RAS/BRAF wild-type mCRC treated in a “real-life” setting, 5FU/LV+anti-EGFR resulted the most adopted, effective, and relatively safe regimen.
Highlights
The introduction of biological agents and the development of continuum of care strategies profoundly changed the treatment landscape for patients with unresectable metastatic colorectal cancer
The eligibility criteria were: age ≥18 years; histologically confirmed diagnosis of CRC originating from the splenic flexure, descending colon, sigma, and rectum; confirmed KRAS, NRAS, and BRAF (V600E) wild-type genotype; and having received a first-line treatment with an antiEGFR-based doublet [FOLFOX or irinotecan/5-fluorouracil/ leucovorin (FOLFIRI)]
The clinical histories of 686 consecutive patients with left-sided RAS and BRAF wild-type metastatic colorectal cancer (mCRC) treated with doublet plus anti-EGFR as first-line regimen were entered
Summary
The introduction of biological agents and the development of continuum of care strategies profoundly changed the treatment landscape for patients with unresectable metastatic colorectal cancer (mCRC). As the maximum benefit is achieved during the first-line treatment, strategies to consolidate the obtained response, maintaining the disease control while keeping a good safety profile, are essential This applies even more with oxaliplatin-based regimens, as peripheral neuropathy could strongly worsen the long-term quality of life of patients [1]. Multiple phase 3 studies have investigated the role of maintenance anti-vascular endothelial growth factor (VEGF) blockade with bevacizumab/fluoropyrimidine following induction chemotherapy in the first-line setting, with variable benefits in terms of PFS and a good safety profile compared to no de-escalation and treatment holidays [2,3,4,5]. Few data regarding post-induction management following first-line antiepidermal growth factor receptor (EGFR)-based doublet regimens in patients with leftsided RAS/BRAF wild-type metastatic colorectal cancer (mCRC) are available
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