Selected Patients With Lung Cancer and Poor Performance Status May Benefit From Standard Therapy

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Patients with poor performance status have an increased incidence of adverse effects from therapy and worse overall outcomes than those with good performance status, but “a selected proportion may still benefit from standard therapy,” according to a review article published in the Journal of the National Comprehensive Cancer Network.

Data on optimal approaches for patients with performance status 2 are lacking, because these patients are underrepresented in conventional clinical trials due to enrollment restrictions, noted the authors, Ajeet Gahra, MD, of the Upstate Medical University and VA Medical Center in Syracuse, New York, and Alissa S. Marr, MD, and Apar Kishor Ganti, MD, MS, of the University of Nebraska Medical Center in Omaha. Available evidence shows, however, that some patients benefit from standard therapy.

“When comorbidities or poor [performance status] exclude surgical interventions for early-stage lung cancer, radiation therapy is the standard alternative” for the management of patients with non–small cell lung cancer (NSCLC). These patients “are often treated with radiation therapy given in a definitive dosing fashion,” the authors stated.

Stereotactic ablative body radiation “is considered biologically more effective at killing cancer cells,” according to the article. “Multiple studies have provided the evidence for the role of [stereotactic ablative body radiation] for NSCLC in medically inoperable candidates” and there is also limited evidence that performance status “does not affect outcomes after [stereotactic ablative body radiation].” The available data led the authors to advocate that “patients with early-stage disease and a marginal lung function should be evaluated in a multidisciplinary setting to determine suitability for limited resection or [stereotactic ablative body radiation]. In the absence of randomized trials, whether one approach is superior to the other is unclear,” the authors added.

Concerning chemotherapy, the authors concluded, “some patients with NSCLC and poor [performance status] may be treated with combination chemotherapy. If this approach is chosen, the preferred treatment is carboplatin with either a taxane or pemetrexed (nonsquamous histology), based on trial data. Single-agent chemotherapy is reasonable to use at the discretion of the treating physician,” the authors continued, but single-agent erlotinib (Tarceva) “should not be used in unselected patients instead of chemotherapy in the first-line setting in the absence of known EGFR mutations.”

They continued, “Patients who are candidates for targeted therapy based on mutation status should be offered a trial of the targeted agent regardless of their performance status. It is unclear how best to implement maintenance therapy strategies in these patients because mature trial data are not currently available.

Small Cell Lung Cancer

Among patients with small cell lung cancer (SCLC), those with poor performance status “seem to have a worse response to chemotherapy,” the authors noted, and the role of concurrent chemoradiation is unclear. “One possible approach may be to try a couple of cycles of systemic chemotherapy, and if the patient tolerates therapy well and experiences an improvement in functional status, radiation could be added concurrently with further chemotherapy cycles,” the researchers wrote. Noting that other factors, including metastases, influence first-line therapy for patients with extensive SCLC, the authors stated that their “practice has been to try systemic chemotherapy in these individuals, because experience has shown that there is a subset of patients whose functional status improves after a decrease in tumor burden after therapy.”

Topotecan is the only therapy approved by the U.S. Food and Drug Administration for relapsed SCLC and, despite a study showing that patients with poor performance status had lower overall survival and slightly greater grade 3/4 anemia, “may be reasonable to use in this setting for this patient cohort,” the authors noted.

“To better define optimal treatment approaches for this population of patients with lung cancer, prospective results are needed for relevant end points, such as rates of treatment completion, functional outcomes, and quality-of-life data,” the authors concluded. ■

Gajra A, Marr AS, Ganti AK: J Natl Compr Canc Netw 12:1015-1025, 2014.