Non-Small Cell Lung Cancer: Stereotactic Radiation Plus Chemo Improved Survival

Dr. Puneeth Iyengar (left) and Dr. Robert Timmerman

Dr. Puneeth Iyengar (left) and Dr. Robert Timmerman Interview with:
Dr. Puneeth Iyengar, MD, PhD
Assistant Professor Director of Clinical Research
Dept of Radiation Oncology Co-leader, Thoracic Disease Oriented Team Harold Simmons Cancer Center
UT Southwestern Medical Center  Dallas, TX

Medical Research: What is the background for this study? What are the main findings?

Response: Stage IV Non-small cell lung cancer (NSCLC) remains a disease of limited survival, in the range of one year for a majority of patients who historically have gone on to receive systemic therapy only. Disease in this patient population most often recurs in the sites of original gross disease. With greater understanding of the biology and patterns of failure that occur in stage IV NSCLC, it is becomingly increasingly obvious that there are subsets of patients, those with limited sites of metastatic disease, who may benefit with more aggressive local therapy in addition to systemic agents to effectuate longer progression free survival (PFS) and potentially overall survival (OS). Since failures of treatment occur most commonly in original gross deposits, local non-invasive therapy in the form of stereotactic body radiation therapy (SBRT) may offer a means to curtail the recurrences, perhaps as a way to shift the time to and patterns of failure.

To address these concepts, a multi institutional single arm phase II study was conducted at UT Southwestern Medical Center in Dallas and University of Colorado Medical Center. Twenty-four patients with limited metastatic NSCLC (fewer than or equal to six sites of disease including the primary) who had progressed through at least one systemic therapy regimen were treated with SBRT to all sites of gross disease and the EGFR inhibitor erlotinib with progression free survival the primary end point. The results of the study were very significant, with a PFS in this study cohort of 14.7 months, compared to historical ranges of 2-4 months, and an OS of 20.4 months, compared to historical ranges of 6-9 months for this same patient population. The SBRT treatments were found to be very safe and efficacious – only 3 out of 47 measurable lesions irradiated recurred with a concomitant shift in failure patterns from local to distant sites. As importantly, EGFR status was evaluated in 13 patient tumors, with none harboring the most common mutations. One could, therefore, predict that with a mutation enriched population, the combination of EGFR inhibitor and SBRT may have offered even greater PFS and OS benefits. Our observations also suggest that the SBRT treatments probably contributed the most to the dramatic PFS and OS outcomes.

These findings were published in the Journal of Clinical Oncology in the December 1, 2014 print issue with an accompanying editorial.

Medical Research: What should clinicians and patients take away from your report? What recommendations do you have for future research as a result of this study?

Response: Non-invasive local treatments like stereotactic body radiation therapy may have a significant role in altering the stage IV NSCLC disease course by offering hope for better PFS and even potentially OS outcomes. SBRT in our study was able to delay time to progression when compared to historical findings and was also able to change patterns of failure, from local to distant sites. Ultimately, stereotactic body radiation therapy may offer a very important therapeutic contribution to the overall management of limited metastatic NSCLC patients.

Our group has proposed a larger study, a phase II randomized trial, that hopes to compare SBRT used after first line therapy plus sequential maintenance therapy versus maintenance therapy alone for limited metastatic NSCLC patients. Similar trials have begun in Europe, suggesting a widespread effort to determine how beneficial local therapies, in the form of SBRT, may be to the metastatic disease state.


Phase II Trial of Stereotactic Body Radiation Therapy Combined With Erlotinib for Patients With Limited but Progressive Metastatic Non-Small-Cell Lung Cancer

Puneeth Iyengar, Brian D. Kavanagh, Zabi Wardak, Irma Smith, Chul Ahn, David E. Gerber, Jonathan Dowell, Randall Hughes, Ramzi Abdulrahman, D. Ross Camidge, Laurie E. Gaspar, Robert C. Doebele, Paul A. Bunn, Hak Choy, and Robert Timmerman

JCO Dec 1, 2014:3824-3830; published online on October 27, 2014;

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Last Updated on April 10, 2015 by Marie Benz MD FAAD