Sandro Pignata1, Giovanni Scambia2, Domenica Lorusso3, Ugo De Giorgi4, Maria Ornella Nicoletto5, Rossella Lauria6, Anna Maria Mosconi7, Cosimo Sacco8, Claudia Omarini9, Pierosandro Tagliaferri10, Gabriella Ferrandina11, Saverio Cinieri12, Antonella Savarese13, Giorgio Valabrega14, Carmela Pisano15, Vanda Salutari16, Francesco Raspagliesi17, Barbara Kopf18, Sabrina Chiara Cecere19, Giulia Amadio16, Giuseppa Maltese20, Marilena Di Napoli21, Stefano Greggi22, Simona Signoriello23, Gennaro Daniele24, Alessandra Sacco25, Simona Losito26, Nicola Normanno27, Francesco Perrone28, Ciro Gallo29, Maria Carmela Piccirillo30. 1. Uro-gynecologic Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, "Fondazione G. Pascale" IRCCS, Napoli, Italy. Electronic address: s.pignata@istitutotumori.na.it. 2. Division of Gynecologic Oncology, Department of Women's and Children's Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy. Electronic address: giovanni.scambia@policlinicogemelli.it. 3. Gynecologic Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy. 4. Medical Oncology Department, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. Electronic address: ugo.degiorgi@irst.emr.it. 5. Department of Oncology, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy. 6. Department of Clinical Medicine and Surgery, Oncology Division, University of Naples Federico II, Naples, Italy. Electronic address: rlauria@unina.it. 7. Medical Oncology, Ospedale S. Maria della Misericordia, Perugia, Italy. 8. Medical Oncology, Ospedale Universitario "S. Maria della Misericordia", Udine, Italy. Electronic address: sacco.cosimo@aoud.sanita.fvg.it. 9. Medical Oncology, Azienda Ospedaliero Universitaria Policlinico, Modena, Italy. 10. Medical Oncology, Università della Magna Grecia, Germaneto (CZ), Italy. Electronic address: tagliaferri@unicz.it. 11. Division of Gynecologic Oncology, Department of Women's and Children's Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy; Ginecologic Oncology, Centro di Ricerca e Formazione ad Alta Tecnologia nelle Scienze Biomediche, Università Cattolica del Sacro Cuore, Campobasso, Italy. 12. Medical Oncology, Ospedale "Senatore Antonio Perrino", Brindisi, Italy. Electronic address: saverio.cinieri@ieo.it. 13. Medical Oncology 1, IRCCS Istituto Nazionale Tumori Regina Elena, Roma, Italy. Electronic address: antonella.savarese@ifo.gov.it. 14. Department of Oncology, Università di Torino e Istituto di Candiolo, FPO, IRCCS, Candiolo (TO), Italy. Electronic address: giorgio.valabrega@ircc.it. 15. Uro-gynecologic Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, "Fondazione G. Pascale" IRCCS, Napoli, Italy. Electronic address: c.pisano@istitutotumori.na.it. 16. Division of Gynecologic Oncology, Department of Women's and Children's Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy. 17. Gynecologic Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy. Electronic address: francesco.Raspagliesi@istitutotumori.mi.it. 18. Medical Oncology Department, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. 19. Uro-gynecologic Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, "Fondazione G. Pascale" IRCCS, Napoli, Italy. Electronic address: s.cecere@istitutotumori.na.it. 20. Gynecologic Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy. Electronic address: Giuseppa.Maltese@istitutotumori.mi.it. 21. Uro-gynecologic Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, "Fondazione G. Pascale" IRCCS, Napoli, Italy. 22. Uro-gynecologic Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, "Fondazione G. Pascale" IRCCS, Napoli, Italy. Electronic address: s.greggi@istitutotumori.na.it. 23. Medical Statistics, Università della Campania Luigi Vanvitelli, Napoli, Italy. Electronic address: simona.signoriello@unicampania.it. 24. Clinical Trial Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, "Fondazione G.Pascale" IRCCS, Napoli, Italy. Electronic address: g.daniele@istitutotumori.na.it. 25. Cell Biology and Biotherapy Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, "Fondazione G.Pascale" IRCCS, Napoli, Italy. 26. Pathology and Citopathology, Istituto Nazionale per lo Studio e la Cura dei Tumori, "Fondazione G.Pascale" IRCCS, Napoli, Italy. Electronic address: n.losito@istitutotumori.na.it. 27. Cell Biology and Biotherapy Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, "Fondazione G.Pascale" IRCCS, Napoli, Italy. Electronic address: n.normanno@istitutotumori.na.it. 28. Clinical Trial Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, "Fondazione G.Pascale" IRCCS, Napoli, Italy. Electronic address: f.perrone@istitutotumori.na.it. 29. Medical Statistics, Università della Campania Luigi Vanvitelli, Napoli, Italy. Electronic address: ciro.gallo@unicampania.it. 30. Clinical Trial Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, "Fondazione G.Pascale" IRCCS, Napoli, Italy. Electronic address: m.piccirillo@istitutotumori.na.it.
Abstract
BACKGROUND: Cervical cancer cells often express Epidermal Growth Factor Receptor (EGFR). Cetuximab (CET), an anti-EGFR antibody, can be safely combined with carboplatin (C) and paclitaxel (P), a standard treatment for advanced/recurrent cervical cancer (ARCC) patients. PATIENTS AND METHODS: ARCC patients, ECOG PS ≤ 1, were randomized to CP for 6 cycles with or without CET (400 mg/m2 one week before starting CP, then 250 mg/m2 weekly) until disease progression or unacceptable toxicity. Event-free survival (EFS) was the primary endpoint. With a 4.5 months expected median EFS and a 6.4 months predicted EFS (HR 0.70), 0.20 one-tailed α and 80% power, 89 events were required for the final intent-to-treat analysis. RESULTS:108 patients were assigned to CP (n = 53) or CP-CET (n = 55). Median age was 50, 69% were PS0, 76% had recurrent disease, 91% had distant metastasis and 57% had received previous chemotherapy. After a median follow-up of 23 months, 102 patients had an event, 97 progressed and 61 died. Median EFS was 4.7 and 6.0 months (one-tail P = 0.43), median PFS was 5.2 and 7.6 months (one-tail P = 0.20) and median OS was 17.7 and 17 months (one-tail P = 0.27), with CP and CP-CET, respectively. There was no difference in the occurrence of severe adverse events, except for skin toxicity. Biomarker analysis, in a small subgroup of patients, suggests that PIK3CA mutation might be predictive of CET resistance. CONCLUSION:CP-CET was not more active than CP alone in unselected ARCC patients.
RCT Entities:
BACKGROUND:Cervical cancer cells often express Epidermal Growth Factor Receptor (EGFR). Cetuximab (CET), an anti-EGFR antibody, can be safely combined with carboplatin (C) and paclitaxel (P), a standard treatment for advanced/recurrent cervical cancer (ARCC) patients. PATIENTS AND METHODS: ARCC patients, ECOG PS ≤ 1, were randomized to CP for 6 cycles with or without CET (400 mg/m2 one week before starting CP, then 250 mg/m2 weekly) until disease progression or unacceptable toxicity. Event-free survival (EFS) was the primary endpoint. With a 4.5 months expected median EFS and a 6.4 months predicted EFS (HR 0.70), 0.20 one-tailed α and 80% power, 89 events were required for the final intent-to-treat analysis. RESULTS: 108 patients were assigned to CP (n = 53) or CP-CET (n = 55). Median age was 50, 69% were PS0, 76% had recurrent disease, 91% had distant metastasis and 57% had received previous chemotherapy. After a median follow-up of 23 months, 102 patients had an event, 97 progressed and 61 died. Median EFS was 4.7 and 6.0 months (one-tail P = 0.43), median PFS was 5.2 and 7.6 months (one-tail P = 0.20) and median OS was 17.7 and 17 months (one-tail P = 0.27), with CP and CP-CET, respectively. There was no difference in the occurrence of severe adverse events, except for skin toxicity. Biomarker analysis, in a small subgroup of patients, suggests that PIK3CA mutation might be predictive of CET resistance. CONCLUSION:CP-CET was not more active than CP alone in unselected ARCC patients.
Authors: Paula M Fracasso; Linda R Duska; Premal H Thaker; Feng Gao; Imran Zoberi; Farrokh Dehdashti; Barry A Siegel; Livnat Uliel; Christine O Menias; Patrice K Rehm; Sherry A Goodner; Allison N Creekmore; Heather L Lothamer; Janet S Rader Journal: Am J Clin Oncol Date: 2022-06-07 Impact factor: 2.787