European journal of cancer (Oxford, England : 1990) · 2025
First-line treatment efficacy of anti-EGFR versus anti-VEGF antibodies in BRAFV600E-mutated metastatic colorectal cancer according to primary tumor sidedness: A pooled analysis of seven clinical trials performed in the first-line treatment of mCRC (German AIO Study Group).
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Weiss Lena, Stintzing Sebastian, Modest Dominik Paul, Stahler Arndt, von Weikersthal Ludwig Fischer, Reinacher-Schick Anke, Decker Thomas, Probst Victoria, Heinrich Kathrin, Schwaner Ingo, Kaiser Florian, Pihusch Rudolf, Fuchs Martin, Held Swantje, Alig Annabel, Gruenberger Birgit, Prager Gerald Werner, Tougeron David, Taieb Julien, Heinemann Volker
Аннотация
BACKGROUND: Both BRAFV600E-mutation and right-sided primary tumor location (PTL), have been associated with poor prognosis in metastatic colorectal cancer (mCRC). The present pooled analysis of individual patient data evaluates the efficacy of first-line chemotherapy combined with anti-EGFR- or anti-VEGF-directed therapy in BRAFV600E-mut mCRC together with PTL.
METHODS: We conducted a pooled analysis of seven first-line AIO-studies (FIRE-3, FIRE-4, FIRE-4.5, CIOX, XELAVIRI, PANAMA, VOLFI) including patients with BRAFV600E-mut and RAS-wild-type mCRC.
RESULTS: Among 209 evaluable patients, left-sided primary tumors (LSPT) were observed in 98 (46.9 %) compared to 111 (53.1 %) patients with right-sided primary tumors (RSPT). In the overall cohort, ORR was comparable (OR 0.85; 95 % CI 0.47-1.52), while median PFS was significantly shorter in patients receiving anti-EGFR-based therapy (HR 1.42; 95 % CI 1.05-1.91; P = 0.022), no major difference was observed with regard to OS (HR 0.96; 95 % CI 0.70-1.32; P = 0.80). Patients with LSPT showed comparable PFS (HR 0.98; 95 % CI 0.63-1.51), but a numerical OS benefit (HR 0.71; 95 % CI, 0.45-1.14) with anti-EGFR- compared to anti-VEGF-based therapy. This effect was observed independent of sex. In contrast, patients with RSPT showed both, inferior PFS (HR 2.09; 95 % CI 1.35-3.22; P < 0.001) and OS (HR 1.31; 95 % CI, 0.84-2.05). These effects were observed in male and female patients.
CONCLUSIONS: The present analysis of BRAFV600E-mut mCRC suggests a survival benefit from anti-EGFR- or anti-VEGF-directed antibodies in patients with LSPT. This effect was not observed in RSPT, where patients showed a clearly greater benefit from bevacizumab.
METHODS: We conducted a pooled analysis of seven first-line AIO-studies (FIRE-3, FIRE-4, FIRE-4.5, CIOX, XELAVIRI, PANAMA, VOLFI) including patients with BRAFV600E-mut and RAS-wild-type mCRC.
RESULTS: Among 209 evaluable patients, left-sided primary tumors (LSPT) were observed in 98 (46.9 %) compared to 111 (53.1 %) patients with right-sided primary tumors (RSPT). In the overall cohort, ORR was comparable (OR 0.85; 95 % CI 0.47-1.52), while median PFS was significantly shorter in patients receiving anti-EGFR-based therapy (HR 1.42; 95 % CI 1.05-1.91; P = 0.022), no major difference was observed with regard to OS (HR 0.96; 95 % CI 0.70-1.32; P = 0.80). Patients with LSPT showed comparable PFS (HR 0.98; 95 % CI 0.63-1.51), but a numerical OS benefit (HR 0.71; 95 % CI, 0.45-1.14) with anti-EGFR- compared to anti-VEGF-based therapy. This effect was observed independent of sex. In contrast, patients with RSPT showed both, inferior PFS (HR 2.09; 95 % CI 1.35-3.22; P < 0.001) and OS (HR 1.31; 95 % CI, 0.84-2.05). These effects were observed in male and female patients.
CONCLUSIONS: The present analysis of BRAFV600E-mut mCRC suggests a survival benefit from anti-EGFR- or anti-VEGF-directed antibodies in patients with LSPT. This effect was not observed in RSPT, where patients showed a clearly greater benefit from bevacizumab.