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.

The MITO CERV-2 trial: A randomized phase II study of cetuximab plus carboplatin and paclitaxel, in advanced or recurrent cervical cancer

De Giorgi U.;Valabrega G.;Normanno N.;Gallo C.;
2019-01-01

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.
2019
153
3
535
540
Cervical cancer; Cetuximab; PIK3CA mutation; Randomized phase 2; Adult; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Cetuximab; Class I Phosphatidylinositol 3-Kinases; Disease Progression; Female; Humans; Middle Aged; Neoplasm Recurrence, Local; Paclitaxel; Progression-Free Survival; Prospective Studies; Response Evaluation Criteria in Solid Tumors; Uterine Cervical Neoplasms
Pignata S.; Scambia G.; Lorusso D.; De Giorgi U.; Nicoletto M.O.; Lauria R.; Mosconi A.M.; Sacco C.; Omarini C.; Tagliaferri P.; Ferrandina G.; Cinier...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1742206
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