دورية أكاديمية
Cetuximab rechallenge plus avelumab in pretreated patients with RAS Wild-type Metastatic Colorectal Cancer: The Phase 2 Single-Arm Clinical CAVE Trial
| العنوان: | Cetuximab rechallenge plus avelumab in pretreated patients with RAS Wild-type Metastatic Colorectal Cancer: The Phase 2 Single-Arm Clinical CAVE Trial |
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| المؤلفون: | Martinelli E., Martini G., Famiglietti V., Troiani T., Napolitano S., Pietrantonio F., Ciardiello D., Terminiello M., Borrelli C., Vitiello P. P., De Braud F., Morano F., Avallone A., Normanno N., Nappi A., Maiello E., Latiano T., Falcone A., Cremolini C., Rossini D., Santabarbara G., Pinto C., Santini D., Cardone C., Zanaletti N., Di Liello A., Renato D., Esposito L., Marrone F., Ciardiello F. |
| المساهمون: | Martinelli, E., Martini, G., Famiglietti, V., Troiani, T., Napolitano, S., Pietrantonio, F., Ciardiello, D., Terminiello, M., Borrelli, C., Vitiello, P. P., De Braud, F., Morano, F., Avallone, A., Normanno, N., Nappi, A., Maiello, E., Latiano, T., Falcone, A., Cremolini, C., Rossini, D., Santabarbara, G., Pinto, C., Santini, D., Cardone, C., Zanaletti, N., Di Liello, A., Renato, D., Esposito, L., Marrone, F., Ciardiello, F. |
| سنة النشر: | 2021 |
| المجموعة: | Sapienza Università di Roma: CINECA IRIS |
| مصطلحات موضوعية: | Antibodie, Monoclonal, Humanized, Cetuximab, Female, Human, Male, Middle Aged, Proto-Oncogene Proteins p21(ras), Antineoplastic Combined Chemotherapy Protocol, Colorectal Neoplasms |
| الوصف: | Importance: Rechallenge therapy with anti-epidermal growth factor receptor (EGFR) drugs has been suggested in patients with chemo-refractory RAS wild-type (WT) metastatic colorectal cancer (mCRC) after initial response to anti-EGFR-based first-line treatment. The association of treatment with cetuximab plus avelumab with overall survival (OS) may be worthy of investigation in this setting. Objective: To assess the efficacy and safety of cetuximab rechallenge therapy plus avelumab. Design, Setting, and Participants: This single-arm, multicenter phase 2 trial enrolled patients from August 2018 to February 2020. Eligible patients with RAS WT mCRC had a complete or partial response to first-line chemotherapy plus anti-EGFR drugs, developed acquired resistance, and failed second-line therapy. Baseline circulating tumor DNA (ctDNA) for KRAS, NRAS, BRAF, and EGFR-S492R mutation analysis was done. Interventions: Patients received avelumab (10 mg/kg every 2 weeks) and cetuximab (400 mg/m2and, subsequently, 250 mg/m2weekly) until disease progression or unacceptable toxic effects. Main Outcomes and Measures: The primary end point was OS. Secondary end points were progression-free survival (PFS), overall response rate (ORR), and safety. Results: Seventy-seven patients were enrolled (42 men, 35 women; median age, 63 years); 71 had microsatellite stable tumors (MSS), 3 microsatellite instability-high tumors (MSI-H), 3 unknown. The study met the primary end point, with median OS (mOS) of 11.6 months (95% CI, 8.4-14.8 months). Median PFS (mPFS) was 3.6 months (95% CI, 3.2-4.1 months). Common grade-3 adverse events were cutaneous eruption, 11 (14%), and diarrhea, 3 (4%). For 67 of 77 (87%) patients, baseline analysis of plasma circulating tumor DNA (ctDNA) for KRAS, NRAS, BRAF, and EGFR-S492R variations was feasible. Forty-eight patients had WT disease, whereas 19 had mutations. Patients with RAS/BRAF WT ctDNA had mOS of 17.3 months (95% CI, 12.5-22.0 months) compared with 10.4 months (95% CI, 7.2-13.6 months) in patients with ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/34382998; info:eu-repo/semantics/altIdentifier/wos/WOS:000684942000006; volume:7; issue:10; firstpage:1529-1535; journal:JAMA ONCOLOGY; https://hdl.handle.net/11573/1641802Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85113152505 |
| DOI: | 10.1001/jamaoncol.2021.2915 |
| الإتاحة: | https://doi.org/10.1001/jamaoncol.2021.2915Test https://hdl.handle.net/11573/1641802Test |
| رقم الانضمام: | edsbas.B9F4D10C |
| قاعدة البيانات: | BASE |
| DOI: | 10.1001/jamaoncol.2021.2915 |
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