Optimal Concurrent Chemoradiotherapy Regimen in Non–Small-Cell Lung Cancer: Prospective, Randomized Data Still Required
Authors: Alfredo Addeo, Charles Comins
Journal: Journal of Clinical Oncology (2015)

Santana-Davila et al 1 conclude that "there is considerable equipoise regarding which [concurrent chemoradiotherapy] regimen should be preferred."The authors support this claim on the basis of a retrospective analysis of a large cohort of patients (n ϭ 1,842) with stage III non-smallcell lung cancer (NSCLC) who received concurrent chemotherapy and radiotherapy (RT) with either cisplatin and etoposide (EP) or carboplatin and paclitaxel (CP).Although concomitant chemotherapy has been accepted worldwide as the preferred treatment, over a sequential one, for patients with NSCLC, 2,3 no randomized clinical trials (RCTs) have compared a specific combination in this setting, 4 and EP had been the regimen used in many RCTs. 2,4Santana-Davila et al, 1 in their study, identified patients with NSCLC treated from 2001 to 2010 and compared the survival rates using Cox proportional hazards regression models with adjustments for confounding provided by propensity score methods and instrumental variables analysis.According to their results, despite some limitations acknowledged by the authors, treatment with CP could represent a possible equivalent alternative in this setting.It is imperative to highlight that in all the RCTs where the regimen containing CP was combined with concomitant RT, the overall survival (OS) was not impressive, 5 and in the only head-to-head RCT, CP versus EP, the OS was inferior. 6o our knowledge, the best available data in an RCT on concurrent CP and RT were published by Bellani et al. 7 In their study, the combination of weekly CP with concomitant RT, followed by consolidation chemotherapy alone (CP), has superior OS compared with the other two arms.However, it was also associated with significantly more adverse effects when compared with the other two arms: grade 3 and 4 leucopenia, 51%; grade 3 and 4 thrombocythemia, 12%; and pulmonary toxicity, 16%.Santana-Davila et al 1 acknowledged some of the study's limitations: no information about dose and RT fractionation; and patients who received CP were more likely to receive consolidation chemotherapy than patients who received EP, leading to possible bias.There was no information about the chemotherapy dose or the number of patients treated within an RCT.Furthermore, they relied on coded administrative data to identify treatment toxicity, but despite this, they claimed that there is equipoise between the two regimens.There is another limitation that further strengthens our skepticism about the study: There is no information on patient staging.Was the positron emission tomography (PET) scan part of the staging tool?We know that, since 2003, the PET scan has been recommended as a complementary staging investigation by the American Society of Clinical Oncology in patients with nonmetastatic NSCLC on computed tomography. 8We know that in this study, Santana-Davila et al 1 analyzed data from 2001 when PET scanning was not routinely available.The use of administrative data sets in health services research can be used to reflect the real world uptake of treatment and disease outcome, but the inference on the OS from uncontrolled comparisons is fraught with selection bias and other biases, including potential confounding by stage migration 9 through newer diagnostic techniques and perhaps even refinements of the staging system. 10e strongly believe there are no short cuts in this setting and, as the authors concede, a phase III RCT is necessary to clarify the best regimen to use along with RT.Although we appreciate the effort the authors made with this article, 1 at the moment, there is no convincing evidence to claim that CP is equivalent to EP in this setting.