PMID- 33751752 OWN - NLM STAT- MEDLINE DCOM- 20210705 LR - 20210705 IS - 1549-490X (Electronic) IS - 1083-7159 (Print) IS - 1083-7159 (Linking) VI - 26 IP - 6 DP - 2021 Jun TI - Safety and Efficacy of Cetuximab-Based Salvage Chemotherapy After Checkpoint Inhibitors in Head and Neck Cancer. PG - e1018-e1035 LID - 10.1002/onco.13754 [doi] AB - BACKGROUND: There are still few data on the activity and safety of cetuximab-based salvage chemotherapy after immunotherapy (SCAI) in patients with squamous cell cancer of the head and neck (SCCHN). MATERIALS AND METHODS: This was a retrospective study of patients with SCCHN who received cetuximab-based SCAI after programmed cell death protein 1 or programmed cell death ligand 1(PD[L]1) inhibitors. Overall response rate (ORR) and disease control rate (DCR) with SCAI and with last chemotherapy before immunotherapy (LCBI) by RECIST 1.1, percentage change from baseline in target lesions (PCTL), progression-free survival (PFS), overall survival (OS), treatment compliance, and toxicity were evaluated. RESULTS: Between March 2016 and November 2019, 23 patients were identified. SCAI consisted of cetuximab-based combinations (3-weekly cisplatin-5FU-cetuximab [n = 2], weekly paclitaxel-cetuximab [n = 17], weekly cisplatin-cetuximab [n = 2], weekly carboplatin-paclitaxel-cetuximab [n = 2]). ORR was 56.5% (11 partial response, 2 complete response). DCR was 78.3%. Among 13 objective responders, median best PCTL was -53.5% (range, -30% to -100%). Median OS and PFS were 12 months and 6 months, respectively. In 10 patients receiving LCBI, ORR to LCBI was 40%, whereas ORR to SCAI achieved 60%. In LCBI-treated patients, median PFS with LCBI was 8 months and median PFS and OS with SCAI were 7 months and 12 months, respectively. Reduced dose intensity of the chemotherapy and cetuximab components occurred in 82.6% and 52.2% of the patients. Grade 1 or 2 adverse events (AEs) occurred in all patients. Grade 3 or 4 AEs developed in 65%, being grade 3 in all of them except in one patient (grade 4 neutropenia). There were no treatment-related deaths. CONCLUSION: Cetuximab-based salvage chemotherapy after PD(L)1 inhibitors associated with high response rates and deep tumor reductions with a manageable safety profile. Subsequent lines of therapy may explain the long survival achieved in our series. These results invite to design studies to elucidate the best therapeutic sequence in patients with SCCHN in the immunotherapy era. IMPLICATIONS FOR PRACTICE: Cetuximab-based salvage chemotherapy (SCAI) achieved high response rates in patients with recurrent/metastatic squamous cell cancer of the head and neck (SCCHN) after progression to PD-1/PD-L1 inhibitors. Objective response rate was higher than and progression-free survival was comparable to that of chemotherapy administered before immunotherapy (IO). In most patients, SCAI consisted of weekly, well-tolerated regimens. These observations have implications for current practice because of the limited evidence to date in SCCHN and the scant therapeutic options in this disease and invite to elucidate which may be the best treatment sequence for patients with head and neck cancer in the IO era. CI - (c) 2021 AlphaMed Press. FAU - Cabezas-Camarero, Santiago AU - Cabezas-Camarero S AUID- ORCID: 0000-0003-4756-7031 AD - Medical Oncology Department, Instituto de Investigacion Sanitaria San Carlos, Hospital Clinico Universitario San Carlos, Madrid, Spain. AD - Centro de Investigacion Biomedica en Red Cancer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain. FAU - Cabrera-Martin, Maria Nieves AU - Cabrera-Martin MN AD - Department Nuclear Medicine, Hospital Clinico Universitario San Carlos, Madrid, Spain. FAU - Merino-Menendez, Salome AU - Merino-Menendez S AD - Department of Radiology, Hospital Clinico Universitario San Carlos, Madrid, Spain. FAU - Paz-Cabezas, Mateo AU - Paz-Cabezas M AD - Medical Oncology Department, Instituto de Investigacion Sanitaria San Carlos, Hospital Clinico Universitario San Carlos, Madrid, Spain. AD - Centro de Investigacion Biomedica en Red Cancer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain. FAU - Garcia-Barberan, Vanesa AU - Garcia-Barberan V AD - Medical Oncology Department, Instituto de Investigacion Sanitaria San Carlos, Hospital Clinico Universitario San Carlos, Madrid, Spain. AD - Centro de Investigacion Biomedica en Red Cancer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain. FAU - Saiz-Pardo Sanz, Melchor AU - Saiz-Pardo Sanz M AD - Department of Pathology, Hospital Clinico Universitario San Carlos, Madrid, Spain. FAU - Iglesias-Moreno, Maricruz AU - Iglesias-Moreno M AD - Department of Otolaryngology-Head and Neck Surgery, Hospital Clinico Universitario San Carlos, Madrid, Spain. FAU - Alonso-Ovies, Almudena AU - Alonso-Ovies A AD - Department of Craniomaxilofacial Surgery, Hospital Clinico Universitario San Carlos, Madrid, Spain. FAU - Perez-Segura, Pedro AU - Perez-Segura P AD - Medical Oncology Department, Instituto de Investigacion Sanitaria San Carlos, Hospital Clinico Universitario San Carlos, Madrid, Spain. AD - Centro de Investigacion Biomedica en Red Cancer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain. LA - eng PT - Journal Article DEP - 20210408 PL - England TA - Oncologist JT - The oncologist JID - 9607837 RN - PQX0D8J21J (Cetuximab) SB - IM MH - *Antineoplastic Combined Chemotherapy Protocols/adverse effects MH - Cetuximab/therapeutic use MH - *Head and Neck Neoplasms/drug therapy MH - Humans MH - Neoplasm Recurrence, Local/drug therapy MH - Retrospective Studies PMC - PMC8176971 OTO - NOTNLM OT - Cetuximab OT - Head and neck cancer OT - Immunotherapy OT - PD-1/PD-L1 inhibitors OT - Salvage chemotherapy COIS- Disclosures of potential conflicts of interest may be found at the end of this article. EDAT- 2021/03/23 06:00 MHDA- 2021/07/06 06:00 PMCR- 2021/06/01 CRDT- 2021/03/22 19:35 PHST- 2020/04/30 00:00 [received] PHST- 2021/02/16 00:00 [accepted] PHST- 2021/03/23 06:00 [pubmed] PHST- 2021/07/06 06:00 [medline] PHST- 2021/03/22 19:35 [entrez] PHST- 2021/06/01 00:00 [pmc-release] AID - ONCO13754 [pii] AID - 10.1002/onco.13754 [doi] PST - ppublish SO - Oncologist. 2021 Jun;26(6):e1018-e1035. doi: 10.1002/onco.13754. Epub 2021 Apr 8.