Antonio Irigoyen1, Javier Gallego2, Carmen Guillén Ponce3, Ruth Vera4, Vega Iranzo5, Inmaculada Ales6, Sara Arévalo7, Aleydis Pisa8, Marta Martín9, Antonieta Salud10, Esther Falcó11, Alberto Sáenz12, José Luis Manzano Mozo13, Gema Pulido14, Joaquina Martínez Galán15, Roberto Pazo-Cid16, Fernando Rivera17, Teresa García García18, Olbia Serra19, Eva Ma Fernández Parra20, Alicia Hurtado21, Ma José Gómez Reina22, Luis Jesús López Gomez23, Esther Martínez Ortega24, Manuel Benavides6, Enrique Aranda14. 1. Virgen de la Salud Hospital, Toledo, Spain. Electronic address: antonioirigoyen@yahoo.com. 2. General Universitario de Elche Hospital, Alicante, Spain. 3. Universitario Ramón y Cajal Hospital, Madrid, Spain. 4. Navarra Hospital, Navarra, Spain. 5. General Hospital, Valencia, Spain. 6. Hospital Regional Universitario y Virgen de la Victoria, Málaga, Spain. 7. Donostia Hospital, Guipúzcoa, Spain. 8. Sabadell Hospital, Corporación Sanitaria Parc Tauli, Barcelona, Spain. 9. Santa Creu i Sant Pau Hospital, Barcelona, Spain. 10. Lleida Arnau de Vilanova Hospital, Lérida, Spain. 11. Fundación Son Llatzer Hospital, Palma de Mallorca, Spain. 12. Clínico Lozano Blesa Hospital, Zaragoza, Spain. 13. Germans Trias i Pujol-ICO Hospital, Barcelona, Spain. 14. Maimonides Institute of Biomedical Research (IMIBIC), Reina Sofía Hospital, University of Córdoba, Spanish Cancer Network (RTICC), Instituto de Salud Carlos III, Córdoba, Spain. 15. Universitario Virgen de las Nieves Hospital, Granada, Spain. 16. Aragon Institute of Biomedical Research (IISA), Miguel Servet University Hospital, Spanish Cancer Network (RTICC), Instituto de Salud Carlos III, Zaragoza, Spain. 17. Marqués de Valdecilla Hospital, Santander, Spain. 18. Morales Meseguer Hospital, Murcia, Spain. 19. Moisés Broggi Hospital, Institut Català Oncologia - Hospitalet del Llobregat, Barcelona, Spain. 20. Nuestra Señora de Valme Hospital, Sevilla, Spain. 21. Fundación Hospital de Alcorcón, Madrid, Spain. 22. Puerta del Mar Hospital, Cádiz, Spain. 23. Virgen de la Salud Hospital, Toledo, Spain. 24. Ciudad de Jaén Hospital, Jaén, Spain.
Abstract
BACKGROUND:Gemcitabine and erlotinib have shown a survival benefit in the first-line setting in metastatic pancreatic cancer (mPC). The aim of this study was to assess whether combining capecitabine (C) with gemcitabine + erlotinib (GE) was safe and effective versus GE in patients with mPC. PATIENTS AND METHODS: Previously untreated mPC patients were randomised to receive G (1000 mg/m2, days 1, 8, 15) + E (100 mg/day, days 1-28) + C (1660 mg/m2, days 1-21) or GE, q4 weeks, until progression or unacceptable toxicity. Primary end-point: progression-free survival (PFS); secondary end-points: overall survival (OS), response rate, relationship of rash with PFS/OS and safety. RESULTS:120 patients were randomised, median age 63 years, ECOG status 0/1/2 33%/58%/8%; median follow-up 16.5 months. Median PFS in the gemcitabine-erlotinib-capecitabine (GEC) and GE arms was 4.3 and 3.8 months, respectively (hazard ratio [HR]: 0.88, 95% confidence interval [CI]: 0.58-1.31; p = 0.52). Median OS in the GEC and GE arms was 6.8 and 7.7 months, respectively (HR: 1.09, 95% CI: 0.72-1.63; p = 0.69). Grade 3/4 neutropenia (GEC 43% versus GE 15%; p = 0.0008) and mucositis (GEC 9% versus GE 0%; p = 0.03) were the only statistically significant differences in grade 3/4 adverse events. PFS and OS were significantly longer in patients with rash (grade ≥1) versus no rash (grade = 0): PFS 5.5 versus 2.0 months (HR = 0.39, 95% CI: 0.26-0.6; p < 0.0001) and OS: 9.5 versus 4.0 months (HR = 0.51, 95% CI: 0.33-0.77; p = 0.0014). CONCLUSION: PFS with GEC was not significantly different to that with GE in patients with mPC. Skin rash strongly predicted erlotinib efficacy. The study was registered with ClinicalTrials.gov: NCT01303029.
RCT Entities:
BACKGROUND:Gemcitabine and erlotinib have shown a survival benefit in the first-line setting in metastatic pancreatic cancer (mPC). The aim of this study was to assess whether combining capecitabine (C) with gemcitabine + erlotinib (GE) was safe and effective versus GE in patients with mPC. PATIENTS AND METHODS: Previously untreated mPCpatients were randomised to receive G (1000 mg/m2, days 1, 8, 15) + E (100 mg/day, days 1-28) + C (1660 mg/m2, days 1-21) or GE, q4 weeks, until progression or unacceptable toxicity. Primary end-point: progression-free survival (PFS); secondary end-points: overall survival (OS), response rate, relationship of rash with PFS/OS and safety. RESULTS: 120 patients were randomised, median age 63 years, ECOG status 0/1/2 33%/58%/8%; median follow-up 16.5 months. Median PFS in the gemcitabine-erlotinib-capecitabine (GEC) and GE arms was 4.3 and 3.8 months, respectively (hazard ratio [HR]: 0.88, 95% confidence interval [CI]: 0.58-1.31; p = 0.52). Median OS in the GEC and GE arms was 6.8 and 7.7 months, respectively (HR: 1.09, 95% CI: 0.72-1.63; p = 0.69). Grade 3/4 neutropenia (GEC 43% versus GE 15%; p = 0.0008) and mucositis (GEC 9% versus GE 0%; p = 0.03) were the only statistically significant differences in grade 3/4 adverse events. PFS and OS were significantly longer in patients with rash (grade ≥1) versus no rash (grade = 0): PFS 5.5 versus 2.0 months (HR = 0.39, 95% CI: 0.26-0.6; p < 0.0001) and OS: 9.5 versus 4.0 months (HR = 0.51, 95% CI: 0.33-0.77; p = 0.0014). CONCLUSION: PFS with GEC was not significantly different to that with GE in patients with mPC. Skin rash strongly predicted erlotinib efficacy. The study was registered with ClinicalTrials.gov: NCT01303029.