Chemotherapy with carboplatin and paclitaxel yielded similar overall survival with fewer adverse effects than did etoposide-plus-cisplatin chemotherapy in the first large study to directly compare the two approaches for stage-3 non–small-cell lung cancer, according to a report published online Nov. 24 in the Journal of Clinical Oncology.
When given concurrently with radiotherapy, the etoposide-based chemotherapy has been considered the most effective for these patients, but the carboplatin combination has recently emerged as an alternative because it is less toxic. Yet, “there is considerable concern that carboplatin plus paclitaxel, although better tolerated than etoposide plus cisplatin, may be inferior in terms of disease control,” said Dr. Rafael Santana-Davila of the University of Washington, Seattle, and his associates.
To compare the two combination chemotherapies, the investigators reviewed the records of 1,842 Veterans Affairs patients (98% men) newly diagnosed as having stage-3 NSCLC during a 10-year period. A total of 27% were treated with the etoposide combination and 73% with the carboplatin combination. In the initial, unadjusted data analysis, etoposide was associated with a longer median survival (17.3 months vs 14.6 months), but further investigation showed that the difference was attributable to patients’ baseline characteristics rather than their chemotherapy regimen.
Since baseline traits differed between the two groups of patients, a subgroup of 381 patients who received etoposide was propensity matched with the same number who received carboplatin. This eliminated baseline differences between the two study groups in age, hemoglobin level, albumin level, percentage of weight loss, and comorbidities. This analysis also demonstrated no survival advantage for etoposide.
The researchers then discovered that some of the medical centers in the study showed definite preferences for or against etoposide, with 8 using the drug more than half the time (in 55%-81% of patients) and 11 using it in fewer than 10% of cases (in 0-9% of patients).
In two final analyses that corrected for this discrepancy, the etoposide combination again carried no survival advantage, compared with the carboplatin combination. Patients who received etoposide plus cisplatin, however, had a higher rate of adverse events during treatment, more oncology visits (mean, 17.6 visits vs. 12.6 for carboplatin), and more hospitalizations during treatment (mean, 2.4 vs 1.7), Dr. Santana-Davila and his associates said (J. Clin. Oncol. 2014 Nov. 24 [doi:10.1200/JCO.2014.56.2587]).
“We believe this study shows that there is considerable equipoise regarding which regimen should be preferred. Given the prevalence of unresectable stage-3 lung cancer, we believe a phase III randomized controlled trial should be considered to definitively answer this question,” they said.
