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Second-line SBRT plus erlotinib extended survival in advanced NSCLC

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December 15, 2014

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.

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PERSPECTIVE
Edward S. Kim

Edward S. Kim

The treatment approach to patients with non–small cell lung cancer (NSCLC) has dramatically changed over the past decade. Approvals for both cytotoxic and biologic agents have introduced the concepts of maintenance therapy [eg, bevacizumab (Avastin, Genentech), pemetrexed (Alimta, Eli Lilly) and erlotinib (Tarceva; Genentech, Astellas)], biomarkers for targeted therapy (eg, ALK and EGFR), and eligibility restrictions based on toxicity or efficacy (eg bevacizumab and pemetrexed in squamous histology). As patients are surviving longer, additional treatment options are considered. This is especially true in selected patients with oligometastatic disease or limited systemic disease.
Stereotactic body radiation therapy (SBRT) is becoming an ever increasing treatment modality for patients with lung cancer. Numerous published reports have demonstrated the safety of SBRT. However, we must be cautious when interpreting data and consider the impact of incorporating limited results into standard clinical patient management.
The study reported by Iyengar and colleagues, a group of highly distinguished investigators in the field of lung cancer at large comprehensive cancer centers, enrolled 24 patients from 2007 to 2013. The trial is a single arm study that examines SBRT in combination with the systemic drug therapy erlotinib, an EGFR tyrosine kinase inhibitor approved for patients after failure of platinum-based chemotherapy.
The results reported are impressive for patients with previously-treated NSCLC. However, it is important to consider the data within the limitations of the study. In this non-randomized study, the population is susceptible to a selection bias, as patients must have good lung function and be amenable to SBRT. As the authors state, in the general NSCLC population, not all patients will have disease that is amenable to SBRT treatment and must have disease that is uncontrolled and spreading rapidly.
When we analyze clinical trials that consist of novel drugs in combination with standard therapy, we know to temper our enthusiasm until the results can be reproduced in a randomized, controlled setting. In these types of trials, the novel drug is not available to patients outside of the trial setting until early phase studies are confirmed and approval is granted. However, the current combination under study – SBRT and erlotinib – is a little different in the sense that SBRT is already utilized outside of the trial setting. In situations such as these, patients in the non-research setting could easily be treated with this combination prior to completion of more definitive trials.
SBRT has certainly added to the treatment options in patients with metastatic NSCLC. However, we must continue to do our due diligence when considering treatments for patients, as there were toxicities attributable to SBRT in this study. Physicians must balance the potential efficacy of adding SBRT to a patient’s treatment plan with the risk of toxicity. Further larger, randomized controlled studies will help elucidate the impact of treatments such as SBRT and guide our clinical decision making in patients with NSCLC.

Edward S. Kim, MD
HemOnc Today Editorial Board member Levine Cancer Institute, Carolinas HealthCare System

Disclosure: Kim reports no relevant financial disclosures.