CT 01 - Clinical Trials Session

LBA3 - Local Consolidative Therapy (LCT) Improves Overall Survival (OS) Compared to Maintenance Therapy/Observation in Oligometastatic Non-Small Cell Lung Cancer (NSCLC): Final Results of a Multicenter, Randomized, Controlled Phase 2 Trial

Sunday, October 21
4:15 PM - 4:25 PM
Location: Stars at Night Ballroom

Local Consolidative Therapy (LCT) Improves Overall Survival (OS) Compared to Maintenance Therapy/Observation in Oligometastatic Non-Small Cell Lung Cancer (NSCLC): Final Results of a Multicenter, Randomized, Controlled Phase 2 Trial
D. R. Gomez1,2, C. Tang3, J. Zhang4, G. R. Blumenschein5, M. Hernandez4, J. J. Lee4, R. Ye6, D. R. Camidge7, F. Skoulidis4, R. Doebele8, L. E. Gaspar9, D. L. Gibbons10, J. Karam4, B. D. Kavanagh9,11, D. A. Palma12, A. V. Louie13, A. Tsao4, B. Sepesi14, S. G. Swisher14, and J. Heymach1; 1The University of Texas MD Anderson Cancer Center, Houston, TX, 2University of Texas MD Anderson Cancer Center, Houston, TX, 3Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, 4MD Anderson Cancer Center, Houston, TX, 5UT Southwestern/Simmons Cancer Center-Dallas, Dallas, TX, 6Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, 7Department of Medical Oncology, University of Colorado, Denver, CO, 8University of Colorado, Aurora, CO, 9Department of Radiation Oncology, University of Colorado Denver, Aurora, CO, 10Department of Thoracic/Head and Neck Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 11University of Colorado, Denver, CO, 12London Health Sciences Centre, London, ON, Canada, 13London Regional Cancer Program, London, ON, Canada, 14Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX

Purpose/Objective(s): We previously observed that LCT improves progression free survival (PFS) in patients with oligometastatic NSCLC after front-line systemic therapy without progression (Gomez et al, Lancet Oncol 2016). Here we report the final analysis of this trial, including the mature secondary endpoint of OS.

Materials/Methods: Patients were enrolled from 3 institutions (MD Anderson Cancer Center, London Health Sciences Center, University of Colorado) and met the following eligibility criteria for randomization: 1) stage IV NSCLC, 2) ≤3 metastatic lesions, 3) ECOG performance status of 2 or less, and 4) no progression after standard front-line systemic therapy. Front-line therapy was four or more cycles of platinum doublet therapy or 3 or more months of EGFR or ALK inhibitors for patients with EGFR mutations/ALK rearrangements, respectively. Patients were then randomized in a 1:1 fashion to receive either standard maintenance therapy/observation (MT/O arm) versus LCT, defined as radiation or surgery to all remaining active sites of disease followed by MT/O (LCT arm). The primary endpoint was PFS, with secondary endpoints including OS, toxicity, and time to appearance of a new lesion. Kaplan-Meier estimates of survival endpoints were obtained, with differences assessed utilizing the log-rank test. Statistical tests were two-sided, and p-values<0.10 were deemed to be significant. At a 10% type I error and a 90% power to detect an improvement in PFS from 4 months (MT/O) to 7 months (LCT), the trial was designed to enroll 94 patients.

Results: The trial was closed by the MD Anderson DSMB after the accrual of 49 patients, due to a benefit detected in PFS; these results have been previously reported at a median follow-up of 12.4 months. For this analysis. median follow-up time for censored patients at the last known date alive is 38.8 months (range 28.3-61.4 months). The PFS benefit was durable, with a median of 14.2 months in the LCT arm (95% CI 7.4,2 4.3) vs. 4.4 months in the MT/O arm (95% CI 2.2, 8.3; p=0.014). The extended follow up also demonstrated a benefit in OS for patients in the LCT arm, with a median OS of 41.2 months (95% CI 18.9, NA) vs. 17.0 months in the MT/O arm (95% CI 10.1, 39.8; p=0.017). No additional Grade 3 or higher toxicities were observed in either arm. Time to new lesion failure trended towards significance with a median of 14.2 months in the LCT arm (95% CI 5.7, 26.2) vs. 6.0 months in the MT/O arm (95% CI 4.4, 8.3; p=0.11).

Conclusion: To our knowledge, this study represents the first randomized data showing an OS benefit for local ablative therapy in patients with oligometastatic NSCLC that do not progress after front-line systemic therapy. Ongoing phase II/III trials will assess the effect of LCT in larger populations and with the incorporation of novel therapeutic agents (immunotherapy, targeted therapy).

Author Disclosure: D.R. Gomez: Research Grant; AstraZeneca, Merck. Honoraria; BMS. Speaker's Bureau; Varian, Merck. Advisory Board; AstraZeneca. C. Tang: None. J. Zhang: None. G.R. Blumenschein: None. M. Hernandez: None. R. Ye: None. R. Doebele: None. L.E. Gaspar: Honoraria; NCI. Treasurer; ASCO. American Joint Commission on Cancer Staging Commit; American College of Surgeons. Co-Chair; NCI. B.D. Kavanagh: Research Grant; Janssen Research & Development. D.A. Palma: Research Grant; Ontario Institute for Cancer Research. Patent/License Fees/Copyright; U.S. Patent Pending. A.V. Louie: Honoraria; Varian Medical Systems Inc. A. Tsao: Advisory Board; BMS, Eli Lilly, Genentech, Roche, Novartis, Ariad, EMD Serono, Merck, Seattle Genetics, Astra-Zeneca, Boehringer-Ingelheim, Sellas Life Science. B. Sepesi: None.

Daniel Gomez, MD

Disclosure:
Employment
MD Anderson Cancer Center - Proton Therapy Center: Associate Professor: Employee

Compensation
AstraZeneca: Advisory Board, Research Grants; BMS: Honoraria; Driver: Travel Expenses; Elekta: Travel Expenses; Merck: Research Grants, Speaker's Bureau; Reflexion: Honoraria; Varian: Speaker's Bureau

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LBA3 - Local Consolidative Therapy (LCT) Improves Overall Survival (OS) Compared to Maintenance Therapy/Observation in Oligometastatic Non-Small Cell Lung Cancer (NSCLC): Final Results of a Multicenter, Randomized, Controlled Phase 2 Trial



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