Predictive factors for 6 vs 12 cycles of Folfiri-Bevacizumab in metastatic colorectal cancer

Abstract

Early switching to de-intensified maintenance regimen is still a matter of debate in metastatic colorectal cancer (mCRC).The MARTHA trial, a S.I.C.O.G. phase III randomized trial, compared FOLOFIRI+bevacizumab (B) for 12 cycles (6 months) followed by B for up to 12 months (FOLFIRI +B*12 arm) vs FOLFIRI+B for 6 cycles (3 months) followed by capecitabine+B for 4 cycles followed by B for up to 12 months (FOLFIRI+B*6 arm). Chemotherapy-naïve mCRC patients were randomized, primary endpoint was progression free survival (PFS), with overall survival (OS) as a secondary endpoint. A novel analysis, the Death Pace Analysis (DPA), was performed to identify patients who benefited from a specific treatment.No PFS difference was seen in 198 enrolled patients (101 in FOLFIRI+B*12, 97 in FOLFIRI+B*6). A non-significant superior OS was observed for FOLFIRI+B*6 (HR 0.74, p 0.098). The DPA demonstrated that 14% of patients were identifiable as FOLFIRI+B*6-benefiting patients. According to a logistic regression analysis including 23 clinicopathological variables, baseline Hb was the only independent predictor of DPA-defined FOLFIRI+B*6-benefit status. Among patients with Hb ≤ 11.1 gr/dL a statistically significant prolonged OS was observed for FOLFIRI+B*6 over FOLFIRI+B*12 (median OS: 20.7 vs 12.6 months, respectively, HR 0.54, p 0.048). No survival difference was observed between arms in patients with Hb > 11.1.mCRC patients with low baseline Hb levels are better treated with FOLFIRI+B*6 first-line strategy. Possible biological explanations for this finding are being investigated.

Time‐varying prognostic value of primary tumor sidedness in metastatic colorectal cancer: A population‐based study and meta‐analysis

“…After contacting the corresponding authors of these studies, 7 additional HRs were received 17‐22 . From an additional 8 studies, the HRs could be retrieved from the Kaplan‐Meier curves 23‐28 . A total of 31 studies were included in the meta‐analysis (Tables S3 and S4).…”

“… 17 , 18 , 19 , 20 , 21 , 22 From an additional 8 studies, the HRs could be retrieved from the Kaplan‐Meier curves. 23 , 24 , 25 , 26 , 27 , 28 A total of 31 studies were included in the meta‐analysis (Tables S3 and S4 ). 14 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 The total number of patients included for the univariable OS analysis was 9558, with 7104 patients in first‐line (22 studies), 1293 in second‐line (3 studies) and 1161 in third‐line or later studies (2 studies).…”

“… 23 , 24 , 25 , 26 , 27 , 28 A total of 31 studies were included in the meta‐analysis (Tables S3 and S4 ). 14 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 The total number of patients included for the univariable OS analysis was 9558, with 7104 patients in first‐line (22 studies), 1293 in second‐line (3 studies) and 1161 in third‐line or later studies (2 studies). Risk of bias plots is displayed in Figure S5 .…”