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)

Weiss, Lena ; Stintzing, Sebastian; Modest, Dominik Paul; Stahler, Arndt; Weikersthal, Ludwig Fischer von; 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 und Heinemann, Volker (2026): 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). In: European Journal of Cancer, Bd. 232, 116105

Abstract

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Klinikum der LMU München > Medizinische Klinik und Poliklinik III (Onkologie)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 09598049
• Sprache: Englisch