Lori J Wirth1, Shaker Dakhil2, Gabriela Kornek3, Rita Axelrod4, Douglas Adkins5, Shubham Pant6, Paul O'Brien7, Philip R Debruyne8, Kelly S Oliner9, Jun Dong9, Swami Murugappan9. 1. Massachusetts General Hospital, Dana-Farber Cancer Institute, Boston, MA, USA. Electronic address: lwirth@mgh.harvard.edu. 2. Cancer Center of Kansas, Wichita, KS, USA. 3. Medizinische Universitaet Wien, Wien, Austria. 4. Thomas Jefferson University Hospital, Philadelphia, PA, USA. 5. Washington University School of Medicine, St. Louis, MO, USA. 6. University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. 7. Medical University of South Carolina, Charleston, SC, USA. 8. Kortrijk Cancer Centre, General Hospital Groeninge, Kortrijk, Belgium; Faculty of Health, Social Care and Education, Anglia Ruskin University, Chelmsford, UK. 9. Amgen Inc., Thousand Oaks, CA, USA.
Abstract
OBJECTIVE: This phase 2 estimation study evaluated docetaxel/cisplatin with/without panitumumab, an anti-epidermal growth factor receptor monoclonal antibody, as first-line therapy for recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Randomized patients received docetaxel/cisplatin (75mg/m(2) each) with/without panitumumab (9mg/kg) in 21-day cycles. Patients randomized to panitumumab+chemotherapy could continue panitumumab monotherapy after completing six chemotherapy cycles without progression; patients randomized to chemotherapy alone could receive second-line panitumumab after progression. Progression-free survival (PFS) was the primary endpoint. Secondary endpoints included overall survival (OS), overall response rate (ORR), time to response (TTR), duration of response (DOR), and safety. A protocol amendment limited enrollment to patients <70years owing to excess toxicity in older patients and added mandatory pegfilgrastim/filgrastim support. Outcomes were also analyzed by human papillomavirus status. RESULTS: 103 of the 113 enrolled patients were evaluable and randomized to receive ⩾1 dose of first-line treatment. Median PFS for panitumumab+chemotherapy was 6.9 (95% CI=4.7-8.3) months versus 5.5 (95% CI=4.1-6.8) months for chemotherapy alone (hazard ratio [HR]=0.629; 95% CI=0.395-1.002; P=0.048). ORR for panitumumab+chemotherapy was 44% (95% CI=31-58%) versus 37% (95% CI=24-51%) for chemotherapy alone (odds ratio [OR]=1.37; 95% CI=0.57-3.33). Median OS for panitumumab+chemotherapy was 12.9 (95% CI=9.4-18.5) months versus 13.8 (95% CI=11.8-22.9) months for chemotherapy alone (HR=1.103; 95% CI=0.709-1.717). Median TTR for panitumumab+chemotherapy treatment was 6.9weeks versus 11.0weeks for chemotherapy alone. Median DOR was 8.0 (95% CI=5.7-11.1) months with panitumumab+chemotherapy versus 5.1 (95% CI=4.4-7.2) months with chemotherapy alone. Grade 3/4 adverse event incidence was 73% with panitumumab+chemotherapy versus 56% with chemotherapy alone. 41% and 55% of patients in the panitumumab+chemotherapy and chemotherapy-alone arms, respectively, received panitumumab monotherapy. CONCLUSION: The addition of panitumumab to docetaxel/cisplatin may improve PFS in recurrent/metastatic SCCHN and has the potential to improve outcomes in these fully, or mostly, active patients.
RCT Entities:
OBJECTIVE: This phase 2 estimation study evaluated docetaxel/cisplatin with/without panitumumab, an anti-epidermal growth factor receptor monoclonal antibody, as first-line therapy for recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Randomized patients received docetaxel/cisplatin (75mg/m(2) each) with/without panitumumab (9mg/kg) in 21-day cycles. Patients randomized to panitumumab+chemotherapy could continue panitumumab monotherapy after completing six chemotherapy cycles without progression; patients randomized to chemotherapy alone could receive second-line panitumumab after progression. Progression-free survival (PFS) was the primary endpoint. Secondary endpoints included overall survival (OS), overall response rate (ORR), time to response (TTR), duration of response (DOR), and safety. A protocol amendment limited enrollment to patients <70years owing to excess toxicity in older patients and added mandatory pegfilgrastim/filgrastim support. Outcomes were also analyzed by human papillomavirus status. RESULTS: 103 of the 113 enrolled patients were evaluable and randomized to receive ⩾1 dose of first-line treatment. Median PFS for panitumumab+chemotherapy was 6.9 (95% CI=4.7-8.3) months versus 5.5 (95% CI=4.1-6.8) months for chemotherapy alone (hazard ratio [HR]=0.629; 95% CI=0.395-1.002; P=0.048). ORR for panitumumab+chemotherapy was 44% (95% CI=31-58%) versus 37% (95% CI=24-51%) for chemotherapy alone (odds ratio [OR]=1.37; 95% CI=0.57-3.33). Median OS for panitumumab+chemotherapy was 12.9 (95% CI=9.4-18.5) months versus 13.8 (95% CI=11.8-22.9) months for chemotherapy alone (HR=1.103; 95% CI=0.709-1.717). Median TTR for panitumumab+chemotherapy treatment was 6.9weeks versus 11.0weeks for chemotherapy alone. Median DOR was 8.0 (95% CI=5.7-11.1) months with panitumumab+chemotherapy versus 5.1 (95% CI=4.4-7.2) months with chemotherapy alone. Grade 3/4 adverse event incidence was 73% with panitumumab+chemotherapy versus 56% with chemotherapy alone. 41% and 55% of patients in the panitumumab+chemotherapy and chemotherapy-alone arms, respectively, received panitumumab monotherapy. CONCLUSION: The addition of panitumumab to docetaxel/cisplatin may improve PFS in recurrent/metastatic SCCHN and has the potential to improve outcomes in these fully, or mostly, active patients.
Authors: Michael Rose; Angela Maurer; Julia Wirtz; Andreas Bleilevens; Tanja Waldmann; Maximilian Wenz; Marie Eyll; Mirja Geelvink; Melanie Gereitzig; Nadine Rüchel; Bernd Denecke; Elke Eltze; Edwin Herrmann; Marieta Toma; David Horst; Tobias Grimm; Stefan Denzinger; Thorsten Ecke; Thomas Alexander Vögeli; Ruth Knuechel; Jochen Maurer; Nadine T Gaisa Journal: Oncogene Date: 2020-09-25 Impact factor: 9.867