SS 04 - Lung 2 - Stage III/IV
35 - Long-Term Results of a Phase I/II Trial of Nelfinavir with Concurrent Chemoradiotherapy for Locally Advanced Non-Small Cell Lung Cancer
Sunday, October 21
5:45 PM - 5:55 PM
Location: Room 301
Ramesh Rengan, MD, PhD
University of Washington
University of Washington: Associate Professor; Medical Director SCCA Proton Center: Employee
Apollo Oncology Group: Advisory Board, Consultant, Honoraria, Travel Expenses; Astra-Zeneca: Consultant
Long-Term Results of a Phase I/II Trial of Nelfinavir with Concurrent Chemoradiotherapy for Locally Advanced Non-Small Cell Lung Cancer
R. Rengan1, R. Mick2, D. A. Pryma3, L. L. Lin4, J. Plastaras5, C. B. Simone II6, A. Gupta5, T. L. Evans7, J. Stevenson8, C. Langer7, J. Kucharczuk9, J. S. Friedberg10, S. Lam5, D. Patsch11, S. M. Hahn12, and A. Maity5; 1University of Washington, Department of Radiation Oncology, Seattle, WA, 2Department of Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA, 3Department of Radiology, University of Pennsylvania, Philadelphia, PA, 4MD Anderson Cancer Center, Division of Radiation Oncology, Houston, TX, 5Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, 6Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, 7Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, PA, 8Division of Hematology and Oncology, Cleveland Clinic Foundation, Cleveland, OH, 9Division of Thoracic Surgery, University of Pennsylvania, Philadelphia, PA, 10Division of Thoracic Surgery, University of Maryland, Baltimore, MD, 11Department of Radiation Oncology, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, 12The University of Texas MD Anderson Cancer Center, Houston, TX
Purpose/Objective(s): The objective of this Phase I/II trial was to determine the response rate by RECIST and the median overall survival (OS) of concurrent chemoradiation (CT-RT) in combination with the radiosensitizer nelfinavir in locally advanced non-small cell lung cancer (LA-NSCLC) compared to historical controls.
Materials/Methods: Nelfinavir (Dose Level (DL) 1: 625mg PO BID, DL2:1250mg PO BID) was administered for 7 to 14 days prior to and during concurrent CT-RT to patients (pts) with biopsy confirmed unresectable IIIA and IIIB NSCLC. 23 patients (65.7%) had stage IIIA disease; 11 patients (31.4%) had stage IIIB disease; 1 patient (2.9%) had a mediastinal recurrence after resection of early stage disease. Median age was 60 years for all patients. 19 patients (54.2%) were male, 16 (45.7%) were female. 10 patients (28.6%) had adenocarcinoma, 16 patients (45.7%) had squamous cell carcinoma; 9 patients (25.7%) had poorly differentiated carcinoma. Patients were treated with concurrent CT-RT to a dose of 66.6/1.8Gy and cisplatinum and etoposide. DLTs were defined as any treatment related Grade 4 hematologic toxicity requiring a break in therapy or non-hematologic Grade ≥ 3 toxicity except esophagitis and pneumonitis. Protocol specified criteria for compliance included receiving greater than 80% of the prescribed RT treatments and 70% of the prescribed nelfinavir doses.
Results: Thirty-five patients were enrolled and met protocol-specified criteria for compliance, 5 at DL1 and 30 at DL2. 2 patients were enrolled and did not meet protocol-specified compliance criteria are excluded from this analysis. No DLTs were observed. The recommended phase II dose of nelfinavir was 1250 mg PO BID. Median follow-up for all patients was 6.8 years and minimum follow-up for survivors was 5 years. No Grade 4 or higher non-hematologic toxicities were observed. Of the non-hematologic toxicities: 10 patients (28%) experienced Grade 3 esophagitis/dysphagia/dehydration; 4 patients (11.4%) experienced Grade 3 nausea; 3 patients (8.5%) experienced Grade 3 anorexia; 3 patients (8.5%) experienced Grade 3 fatigue; and 1 patient (3%) experienced grade 3 diarrhea and 1 patient (3%) experienced grade 3 dyspnea. 33 of the 35 patients had evaluable post-treatment CT with RECIST response rate of 94% and (31/33) stable disease rate of 6% (2/33). The cumulative incidence of local failure as site of first failure was 20%, with the median time to failure not reached (NR). The cumulative incidence of distant failure as site of first failure was 51%, with the median time to distant failure of 15.8 months. The median progression-free survival was 12 months. The median OS for all patients was 40 months; 5 year OS was 37%.
Conclusion: Nelfinavir administered with concurrent CT-RT is associated with acceptable toxicity and very promising local control, overall response rate, and survival in unresectable LA-NSCLC. These data suggest that nelfinavir may enhance the efficacy of chemo-RT in this disease.
Author Disclosure: R. Rengan: Honoraria; Apollo Oncology Group. Consultant; Apollo Oncology Group, Astra-Zeneca. Advisory Board; Apollo Oncology Group. Travel Expenses; Apollo Oncology Group. R. Mick: None. D.A. Pryma: Research Grant; IBA Molecular, Molecular Insight Pharmaceuticals, Siemens. Honoraria; IBA Molecular, Siemens. Consultant; Molecular Insight Pharmaceuticals. Nuclear Oncology Council Board Member; Society of Nuclear Medicine and Molecular Imaging. L.L. Lin: Employee; VA Hospital. J. Plastaras: None. C.B. Simone: Employee; Nemours/Alfred I. duPont Hospital for Children. Chair, Executive Council; Chair, Lung Committee; Proton Collaborative Group (PCG). Editor-in-Chief; Annals of Palliative Medicine. Chair, Lung Resource Panel; American Society for Radiation Oncology. A. Gupta: None. T.L. Evans: Employee; Lankenau Institute for Medical Research. Honoraria; Celgene, Genentech, Lilly. Consultant; Celgene, Genentech, Lilly. Advisory Board; Celgene, Genentech, Lilly. Travel Expenses; Genentech, Lilly. Stock; Immunome. C. Langer: Honoraria; BMS. Consultant; BMS, Celgene, Genentech, Lilly. Advisory Board; Abbott, BMS, Celgene, Genentech, Lilly, Synta. Vice Chair; RTOG. J. Kucharczuk: None. J.S. Friedberg: None. S. Lam: None. D. Patsch: None. S.M. Hahn: Honoraria; AACR, Academic Institutions, UCSF Radiation Oncology External Advisory Board, UCSF Cancer Center External Advisory Board. Travel Expenses; AACR, Academic Institutions, UCSF Radiation Oncology External Advisory Board, UCSF Cancer Center External Advisory Board. Partnership; Liquid Biotech. Royalty; NIH/Mitos Inc. Patent/License Fees/Copyright; Liquid Biotech. VC Educational Council; ASTRO Board of Directors.