Second-line SBRT plus erlotinib extended survival in advanced NSCLC
Treatment with stereotactic body radiation therapy and erlotinib appeared highly effective in patients with metastatic stage IV non–small cell lung cancer who progressed on prior platinum-based chemotherapy, according to results of a single-arm phase 2 study.
Patients with stage IV NSCLC who progress on first-line chemotherapy historically demonstrate poor survival outcomes, and they typically fail in original sites of gross disease, according to background information provided by researchers.
Puneeth Iyengar, MD, PhD, assistant professor of radiation oncology at UT Southwestern Medical Center, and colleagues hypothesized that stereotactic body radiation therapy (SBRT) may help systemic agents delay relapse.
Iyengar and colleagues evaluated PFS, OS and other outcomes among 24 patients (median age, 67 years) who underwent second- or later-line treatment with SBRT plus erlotinib (Tarceva; Genentech, Astellas).
Patients had stage IV NSCLC with no more than six sites of extracranial disease. Fifteen patients had failed first-line therapy, seven failed second-line therapy and two failed third-line therapy.
Sixteen of 24 patients received SBRT to more than one site. The site most often irradiated was the lung parenchyma. Mean follow-up was 16.8 months.
Researchers reported median PFS of 14.7 months and median OS of 20.4 months.
“Most patients progressed in new distant sites, with only three of 47 measurable lesions recurring within the SBRT field,” Iyengar and colleagues wrote.
Researchers observed an association between the number of SBRT-treated sites and a higher rate for mortality (P=.04; HR=1.51). For each additional site treated, results showed a 1.5-fold increase in likelihood for mortality.
Patients who received intrathoracic treatment demonstrated a reduced chance for progression compared with those who received extrathoracic therapy (P=.018; HR=0.08).
Researchers reported four grade 4 toxicities and 13 grade 5 toxicities. They determined two of those toxicities — one grade 4 and one grade 5 — potentially were related to SBRT.
“A median PFS of 14.7 months and an OS of 20.4 months in a group of patients who historically have done poorly encourage consideration of a new treatment paradigm with the inclusion of aggressive noninvasive local therapy in the form of stereotactic body radiation therapy,” Iyengar and colleagues wrote.
SBRT appears to be a logical choice when striving to treat multiple sites of oligometastases, but the toxicity caused by ablative therapies — although generally uncommon — can be significant, Salma K. Jabbour, MD, assistant professor of radiation oncology at Rutgers Cancer Institute of New Jersey, wrote in an accompanying editorial.
“The identification of patients who are most likely to benefit from radiation therapy to multiple metastases relies on the selection of those patients who have been treated with first-line chemotherapy and have maintained their performance status,” Jabbour wrote. “As patients may live longer and respond better to systemic therapies, this clinical scenario introduces a more pressing need for radiation therapy to build on the gains of targeted agents. Iyengar [and colleagues] show that SBRT can target multiple sites for limited, nonbrain metastases in NSCLC with a reasonable toxicity profile and escalated radiation doses; the resultant implication is that local control may be achieved in a noninvasive fashion, can delay disease progression and the use of other therapies; and may improve survival.”
For more information:
- Iyengar P. J Clin Oncol. 2014;doi:10.1200/JCO.2014.56.7412.
- Jabbour SK. J Clin Oncol. 2014;doi:10.1200/JCO.2014.58.5539.
Disclosure: The researchers report research funding from, consultant or advisory roles with, speakers’ bureau roles with, stock ownership in and travel expenses from several pharmaceutical companies, including AstraZeneca, Bayer, Boehringer Ingelheim, Celgene, Genentech, Lilly, MedImmune, Pfizer and Roche.