ASTRO 2017: Adding Radiation to Maintenance Chemotherapy May Benefit Patients With Limited Metastatic NSCLC

Key Points

  • The interim analysis reported a median progression-free survival rate of 9.7 months with consolidative radiation therapy added to maintenance chemotherapy compared to 3.5 months for maintenance chemotherapy alone.
  • At the time of analysis, 4 of 14 patients receiving radiation plus maintenance chemotherapy had progressed compared to 10 of 15 patients receiving maintenance chemotherapy-only.
  • Confirmation of the results in a larger prospective trial is warranted.

For patients with limited metastatic non–small cell lung cancer (NSCLC), adding radiation therapy before maintenance chemotherapy may curb disease progression when compared to maintenance chemotherapy alone, according to a randomized phase II clinical trial reported by Iyengar et al. at the 59th Annual Meeting of the American Society for Radiation Oncology (ASTRO) (Abstract LBA-3).

Progression-free survival in the trial increased from 3.5 months to 9.7 months with the addition of radiation therapy delivered to all the metastatic sites of lung cancer, as well as the primary disease site. Treatment-related side effects were similar for the two treatment approaches.

Study Details

The study was a randomized phase II trial testing whether the addition of local treatment, in the form of consolidative radiation therapy, to the standard treatment of systemic therapy improved progression-free survival for patients with limited metastatic NSCLC. Eligible patients included those with stage IV disease that had metastasized to six or fewer sites, including the primary tumor site, who responded at least partially to first-line/induction chemotherapy.

Patients were randomly assigned to receive either maintenance chemotherapy alone (15 patients) or a combination of stereotactic ablative radiotherapy (SAbR) to all sites of disease followed by maintenance chemotherapy (14 patients). Radiation to metastases was offered as a single fraction (to 21–27 Gray (Gy)), three fractions (to 26.5–33 Gy), or five fractions (to 30–37.5 Gy) of SAbR (regimens were biologically equivalent). Radiation to the primary disease site was delivered to a total dose of 45 Gy via SAbR where possible, or through 15 fractions of hypofractionated radiation therapy if the primary tumor was too central or involved mediastinal nodes.

Maintenance chemotherapy was left to the discretion of the treating medical oncologists and consisted of pemetrexed, docetaxel, erlotinib, or gemcitabine.

Between April 2014 and July 2016, a total of 29 patients were accrued to the trial. The median patient age was 70 years (range 51–79 years) for  patients receiving maintenance chemotherapy only and 63.5 years (range 51–78) for those receiving SAbR followed by maintenance chemotherapy. Most patients were male (69%), and 86% of patients had tumors with nonsquamous histologies. In the 14 patients who received local therapy, 31 lesions were treated with radiation.

The median follow-up for this report was 9.6 months (range 2.4–30.2 months). Patient accrual was stopped ahead of schedule after an unplanned interim analysis found substantially improved survival rates in the arm receiving local therapy, matching similar findings in a parallel trial.

Interim Analysis Findings

The interim analysis found a median progression-free survival rate of 9.7 months with consolidative radiation therapy followed by chemotherapy vs 3.5 months for maintenance chemotherapy alone (P = .01; Hazard Ratio (HR) = 0.304, 95% CI 0.113–0.815). Survival rates were estimated using the Kaplan-Meier method and compared using the log-rank test and Cox proportional hazard models.

Specifically, rates of local control and delay in distant metastases also favored the approach incorporating radiation with systemic therapy. There were no recurrences in original sites of gross disease vs seven failures in original sites of gross disease in the arm receiving only maintenance therapy. At the time of analysis, 4 of 14 patients who received radiation plus maintenance chemotherapy had progressed vs 10 of 15 patients receiving only maintenance chemotherapy. None of the recurrences among the patients receiving radiation plus chemotherapy were in areas treated directly with radiation therapy.

Treatment-related side effects were similar between the two treatment arms. There was one grade 4 toxicity in the group receiving radiation plus maintenance chemotherapy vs two grade 3 toxicities and one grade 4 toxicity in the group receiving only maintenance chemotherapy.

Commentary

“Even in the era of immunotherapy, there are not large numbers of metastatic NSCLC patients with durable responses to systemic therapy. In our trial, however, the addition of radiation therapy directed at each of the cancerous areas greatly improved how patients responded to subsequent rounds of chemotherapy,” said Puneeth Iyengar, MD, PhD, lead author of the study and an Assistant Professor of Radiation Oncology at the University of Texas Southwestern Medical Center. “This finding suggests that local treatments, including radiation, could work in concert with chemotherapy to prolong the amount of time before recurrence occurs in patients with limited sites of metastatic NSCLC.”

“Moreover, the addition of consolidative radiation did not increase toxicity, which allowed patients to continue on to additional systemic therapy that is important to controlling aggressive metastatic disease,” said Dr. Iyengar.

A larger, randomized phase III trial is planned to test progression-free survival as well as overall survival. While results indicate a clear benefit of adding local therapy for the management of limited metastatic NSCLC, Dr. Iyengar stressed the need for confirmation in a larger prospective trial.

 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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