Consolidative Radiation Therapy: New Paradigm for Limited Metastatic NSCLC?


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Puneeth Iyengar, MD, PhD

Puneeth Iyengar, MD, PhD

ADDING CONSOLIDATIVE RADIATION therapy to maintenance chemotherapy had a robust effect on preventing disease progression compared with maintenance chemotherapy alone in patients with limited metastatic non–small cell lung cancer (NSCLC), according to a late-breaking study presented at the 2017 Annual Meeting of the American Society for Radiation Oncology (ASTRO).1 

In the phase II study, patients with limited metastatic NSCLC treated with radiotherapy plus maintenance chemotherapy had a median progression-free survival of 9.7 months, whereas median progression-free survival was 3.5 months with maintenance chemotherapy alone. Importantly, radiation did not substantially increase toxicities. 

The study was halted prematurely after an interim analysis found that progression-free survival was almost tripled in the radiotherapy/chemotherapy arm. Larger ongoing phase III studies are determining the impact of this approach on overall survival. 

“Up to 70% of patients with NSCLC will respond to cytotoxic chemotherapy, which is the standard approach, but in most patients, disease progression occurs 3 to 4 months after treatment. About two-thirds of patients whose disease returns have progression only at sites where disease was present prior to the start of induction therapy. For our study, we hypothesized that patients with limited metastatic disease would have progression-free survival outcomes similar to those with more widespread disease,” explained lead author Puneeth Iyengar, MD, PhD, of The University of Texas Southwestern Medical School, Dallas. “Therefore, we wanted to improve the potential durability of treatment response in a subset of patients with limited metastatases by adding local therapy to maintenance chemotherapy regimens.” 

Study Details 

PATIENTS ENTERED IN THE TRIAL had previously untreated NSCLC and six or fewer sites of metastatic disease. All patients received first-line chemotherapy, and those with a partial response or stable disease were randomized to receive maintenance chemotherapy or stereotactic body radiation therapy to all metastatic sites and primary cancer (if feasible) or hypofractionated radiation therapy to the primary tumor (if it was central and/or involved mediastinal lymph nodes) followed by maintenance chemotherapy. The interim analysis was conducted after 15 patients were treated on the arm receiving maintenance chemotherapy alone, and 14 patients were treated on the arm receiving radiation plus maintenance chemotherapy; 29 patients were evaluable. 

RADIOTHERAPY PLUS CHEMOTHERAPY FOR METASTATIC NSCLC

  • Adding radiation to maintenance chemotherapy in patients with advanced NSCLC nearly tripled the proportion of patients who were free of disease progression.
  • The strategy did not add significant toxicity.
  • If phase III trials show an overall survival advantage, it may become a new standard of care.

The 6.2-month absolute difference in median progression-free survival represented a significant 70% improvement favoring the addition of radiation therapy (P = .01). In the maintenance chemotherapy–alone arm, more patients had treatment failure and more had treatment failure earlier, Dr. Iyengar noted. 

Patterns of Failure 

ONLY 4 OF 14 PATIENTS who received local radiation plus maintenance chemotherapy had disease progression (5 sites) compared with 10 of 15 in the maintenance chemotherapy–alone arm (13 sites). Of the 13 treatment failure sites, 8 occurred in the lung in the chemotherapy arm, whereas all 5 treatment failures in the radiation-containing arm were at distant sites. 

“We saw a shift in the pattern of failure from local to distant sites with the addition of radiation. Patients receiving local therapy had no failures in areas that were irradiated, whereas the chemotherapy arm had failures in sites that would have been irradiated,” he continued. 

Dr. Iyengar pointed out that the median progression-free survival of 3.5 months in the maintenance chemotherapy arm is similar to that of historical findings for patients with widely metastatic disease. “Patients with NSCLC treated only with systemic therapy have a similar progression-free survival whether metastases are widely dispersed or limited. Our goal is to achieve more durable responses,” he told listeners. 

“In our understanding of disease spread, local control [with radiotherapy] appears to help regulate patterns and timing of disease progression and metastatic dissemination,” Dr. Iyengar noted. 

There was no significant difference in toxicity between the two study arms. ■

DISCLOSURE: Dr. Iyengar reported no conflicts of interest. 

REFERENCE 

1. Iyengar P, Tumati V, Gerber D, et al: Consolidative radiotherapy for limited metastatic non–small cell lung cancer: A randomized phase II trial. 2017 ASTRO Annual Meeting. Abstract LBA-3. Presented September 24, 2017.


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BRIAN G. CZITO, MD, a radiation oncologist at Duke Cancer Institute in Durham, North Carolina, commented on the study presented by Iyengar et al at the 2017 American Society for Radiation Oncology Annual Meeting. 

“This study of focal high-dose radiation in stage IV...


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