PIK3CA Pathway Mutations Predictive of Poor Response Following Standard Radiochemotherapy ± Cetuximab in Cervical Cancer Patients
| Autor: | Anne de la Rochefordière, Ivan Bièche, Virginie Fourchotte, Florence Joly, Emmanuel Sevin, Béatrice Weber, Mathieu Minsat, Benard Asselain, Anne Floquet, Maud Kamal, Suzy Scholl, Maud Aumont, Quentin Leroy, Laurence Thomas, Marius Pop, Alhassane Diallo, Sophie Maillard, Hervé Curé, Michel Fabbro, Peter Petrow, Philippe Beuzeboc, Thierry Petit, K. Peignaux, Laurence Gladieff, Corine Plancher, Laurence Gonzague, Virginie Bernard, Claire Brunaud, Christine Kerr, Dominique Berton-Rigaud, AnaTereza Nadan, Sebastien Armanet, Audrey Margogne |
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| Rok vydání: | 2015 |
| Předmět: |
Adult
Oncology Cancer Research medicine.medical_specialty Class I Phosphatidylinositol 3-Kinases Cetuximab Uterine Cervical Neoplasms Protein Serine-Threonine Kinases medicine.disease_cause Disease-Free Survival Proto-Oncogene Proteins p21(ras) Phosphatidylinositol 3-Kinases AMP-Activated Protein Kinase Kinases Maintenance therapy Proto-Oncogene Proteins Internal medicine medicine Humans neoplasms Aged Cervical cancer business.industry Standard treatment Head and neck cancer Cancer Chemoradiotherapy Middle Aged medicine.disease Mutation ras Proteins Female KRAS Cisplatin business Signal Transduction medicine.drug |
| Zdroj: | Clinical Cancer Research. 21:2530-2537 |
| ISSN: | 1557-3265 1078-0432 |
| DOI: | 10.1158/1078-0432.ccr-14-2368 |
| Popis: | Purpose: EGFR is frequently overexpressed in cervical cancer, suggesting EGFR blockade as a promising treatment approach. Cetuximab, an anti EGFR antibody, used conjointly with radiochemotherapy, was feasible in first-line treatment of cervix carcinoma limited to the pelvis. Experimental Design: This randomized phase II trial enrolled 78 FIGO stage IB2–IIIB cervical cancer patients to either cisplatin-based radiochemotherapy alone (arm B, n = 38) or conjointly with a 6-week course of weekly cetuximab (arm A, n = 40). Brachytherapy was given to the pelvic mass. Primary endpoint was disease-free survival (DFS) at 2 years. EGFR expression and targeted sequencing were performed in 54 of 78 patients. Results: Cetuximab over a 6-week period did not improve DFS at 24 months. At 31 months median follow-up, DFS was not significantly different (P = 0.18). Complete response at 4 to 6 months was strongly predictive for excellent DFS (log-rank test; P < 0.001). PIK3CA, KRAS, and STK11 mutations were observed in 22%, 4%, and 2% of patients, respectively. No tumor with a PI3K pathway mutation showed complete response (0/8 in arm A and 0/6 in arm B), whereas 14 of 52 (27%) tumors without mutations did (P = 0.021). PI3K pathway-mutated tumors showed a trend toward poorer DFS (P = 0.06) following cetuximab (8/22) as compared with those following standard treatment only (6/18). Conclusions: Similar to patients with head and neck cancer, patients with cervical cancer showed no gain in DFS at 2 years following a combined treatment of cetuximab with radiochemotherapy. Although treatment tolerance and compliance were satisfactory, it remains to be demonstrated whether maintenance therapy with cetuximab could be beneficial in selected patient groups. Clin Cancer Res; 21(11); 2530–7. ©2015 AACR. |
| Databáze: | OpenAIRE |
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