E Aranda1, P García-Alfonso2, M Benavides3, A Sánchez Ruiz4, C Guillén-Ponce5, M J Safont6, J Alcaide7, A Gómez8, R López9, J L Manzano10, M Méndez Ureña11, J Sastre12, F Rivera13, C Grávalos14, T García15, J I Martín-Valadés16, E Falcó17, M Navalón18, E González Flores19, A Ma García Tapiador20, A Ma López Muñoz21, E Barrajón22, M Reboredo23, P García Teijido24, A Viudez25, N Cárdenas26, E Díaz-Rubio12. 1. IMIBIC, Reina Sofía Hospital, University of Córdoba, CIBERONC, Instituto de Salud Carlos III, Spain. Electronic address: earanda@seom.org. 2. Hospital Universitario Gregorio Marañón, Madrid, Spain. 3. Hospital Universitario Regional y Virgen de la Victoria, Málaga, Spain. 4. Hospital Universitario Puerta de Hierro, Madrid, Spain. 5. IRYCIS, CIBERONC, Alcalá University, Hospital Universitario Ramón y Cajal, Madrid, Spain. 6. Hospital General Universitario de Valencia, Valencia, Spain. 7. Hospital Costa del Sol, Málaga, Spain. 8. IMIBIC, Reina Sofía Hospital, University of Córdoba, CIBERONC, Instituto de Salud Carlos III, Spain. 9. Hospital Clínico Universitario de Santiago, A Coruña, Spain. 10. Institut Català d'Oncologia, Hospital Germans Trias i Pujol, Barcelona, Spain. 11. Hospital de Móstoles, Madrid, Spain. 12. Hospital Universitario Clínico San Carlos, Instituto de Investigación Hospital Clínico San Carlos (IdISSC), University Complutense, CIBERONC, Madrid, Spain. 13. Hospital Universitario Marqués de Valdecilla, Santander, Spain. 14. Hospital 12 de Octubre, Madrid, Spain. 15. Hospital Morales Meseguer, Murcia, Spain. 16. Fundación Jiménez Díaz, Madrid, Spain. 17. Hospital Son Llàtzer, Palma de Mallorca, Spain. 18. Complejo Asistencial de Zamora, Zamora, Spain. 19. Hospital Virgen de las Nieves, Granada, Spain. 20. Complejo Hospitalario La Mancha Centro, Ciudad Real, Spain. 21. Hospital Universitario de Burgos, Burgos, Spain. 22. Hospital Clínica Benidorm, Alicante, Spain. 23. Complejo Hospitalario Universitario A Coruña, A Coruña, Spain. 24. Hospital San Agustín, Avilés, Spain. 25. Complejo Hospitalario de Navarra, Pamplona, Spain. 26. Complejo Hospitalario de Jaén, Jaén, Spain.
Abstract
BACKGROUND: This multicentre, randomised, and phase II study evaluated mFOLFOX+cetuximab followed by maintenance mFOLFOX+cetuximab or single-agent cetuximab in metastatic colorectal cancer (mCRC) patients (NCT01161316). PATIENTS AND METHODS: Previously, untreated mCRC patients (wild-type KRAS) were randomised to receive cetuximab+mFOLFOX-6 (8 cycles for 2 weeks) followed by maintenance therapy: single-agent cetuximab (Arm-A) or mFOLFOX-6 + cetuximab (Arm-B) until progression. Primary endpoint was progression-free survival (PFS) at 9 months. RESULTS:One hundred ninety-three patients (median [range] age 60 [33-74] years) were randomised (2:1): 129 Arm-A versus 64 Arm-B. PFS at 9 months (95% confidence interval) showed non-inferiority between arms (Arm-A/Arm-B: 60 [52, 69]%/72 [61, 83]%, p [non-inferiority]<0.1). There were no statistically significant differences in the PFS (Arm-A/Arm-B: 9 [95% CI 7, 10] months/10 [7,13] months, hazard ratio [HR] = 1.19 [0.80, 1.79]) or overall survival (23 [19, 28] months/27 [18, 36] months, HR = 1.24 [0.85, 1.79]) between arms. The objective response rate was also similar (48 [39, 57]%/39 [27, 52]%). The safety profile was similar between arms, and all patients experienced at least one adverse event (AE) (Arm-A/Arm-B grade ≥III AEs: 70%/68%). The most common grade ≥III AEs were as follows: neutropenia (Arm-A/Arm-B: 28%/26%), rash acneiform (15%/24%) and sensory neuropathy (2%/15%) in any group. Arm-A was associated with less grade ≥III rash and sensory neuropathy and a lower rate of serious AEs (20%/27%). CONCLUSION(S): This phase II exploratory trial with a non-inferiority design suggests that maintenance therapy with single-agent cetuximab following mFOLFOX+cetuximab induction could be a valuable option compared with mFOLFOX+cetuximab treatment continuation. We await phase III trials to confirm single-agent cetuximab as maintenance therapy in mCRC patients.
RCT Entities:
BACKGROUND: This multicentre, randomised, and phase II study evaluated mFOLFOX+cetuximab followed by maintenance mFOLFOX+cetuximab or single-agent cetuximab in metastatic colorectal cancer (mCRC) patients (NCT01161316). PATIENTS AND METHODS: Previously, untreated mCRC patients (wild-type KRAS) were randomised to receive cetuximab+mFOLFOX-6 (8 cycles for 2 weeks) followed by maintenance therapy: single-agent cetuximab (Arm-A) or mFOLFOX-6 + cetuximab (Arm-B) until progression. Primary endpoint was progression-free survival (PFS) at 9 months. RESULTS: One hundred ninety-three patients (median [range] age 60 [33-74] years) were randomised (2:1): 129 Arm-A versus 64 Arm-B. PFS at 9 months (95% confidence interval) showed non-inferiority between arms (Arm-A/Arm-B: 60 [52, 69]%/72 [61, 83]%, p [non-inferiority]<0.1). There were no statistically significant differences in the PFS (Arm-A/Arm-B: 9 [95% CI 7, 10] months/10 [7,13] months, hazard ratio [HR] = 1.19 [0.80, 1.79]) or overall survival (23 [19, 28] months/27 [18, 36] months, HR = 1.24 [0.85, 1.79]) between arms. The objective response rate was also similar (48 [39, 57]%/39 [27, 52]%). The safety profile was similar between arms, and all patients experienced at least one adverse event (AE) (Arm-A/Arm-B grade ≥III AEs: 70%/68%). The most common grade ≥III AEs were as follows: neutropenia (Arm-A/Arm-B: 28%/26%), rash acneiform (15%/24%) and sensory neuropathy (2%/15%) in any group. Arm-A was associated with less grade ≥III rash and sensory neuropathy and a lower rate of serious AEs (20%/27%). CONCLUSION(S): This phase II exploratory trial with a non-inferiority design suggests that maintenance therapy with single-agent cetuximab following mFOLFOX+cetuximab induction could be a valuable option compared with mFOLFOX+cetuximab treatment continuation. We await phase III trials to confirm single-agent cetuximab as maintenance therapy in mCRC patients.
Authors: Dominik Paul Modest; Meinolf Karthaus; Stefan Fruehauf; Ullrich Graeven; Lothar Müller; Alexander Otto König; Ludwig Fischer von Weikersthal; Karel Caca; Albrecht Kretzschmar; Eray Goekkurt; Siegfried Haas; Annika Kurreck; Arndt Stahler; Swantje Held; Armin Jarosch; David Horst; Anke Reinacher-Schick; Stefan Kasper; Volker Heinemann; Sebastian Stintzing; Tanja Trarbach Journal: J Clin Oncol Date: 2021-09-17 Impact factor: 44.544
Authors: Amanda N Lisby; John C Flickinger; Babar Bashir; Megan Weindorfer; Sanjna Shelukar; Madison Crutcher; Adam E Snook; Scott A Waldman Journal: Expert Rev Precis Med Drug Dev Date: 2021-02-02