Elsevier

Lung Cancer

Volume 108, June 2017, Pages 173-182
Lung Cancer

A population-based comparative effectiveness study of chemoradiation regimens and sequences in stage III non-small cell lung cancer

https://doi.org/10.1016/j.lungcan.2017.03.017Get rights and content

Highlights

  • Chemoradiation is used to treat many patients with stage III NSCLC.

  • Carboplatin- and cisplatin-containing regimens resulted in similar outcomes.

  • Consolidation chemotherapy after concurrent chemoradiation improved survival.

  • Consolidation chemotherapy only benefited patients treated with carboplatin.

  • When using carboplatin, consolidation chemotherapy should be considered.

Abstract

Objectives

In patients receiving concurrent chemoradiation for locally advanced non-small cell lung cancer (NSCLC), consolidation chemotherapy is frequently given even though several randomized trials have failed to show a benefit. We explored the potential benefits of consolidation chemotherapy using a population-based comparative effectiveness approach.

Materials and methods

Surveillance, Epidemiology, and End Results-Medicare was used to identify patients with Stage III NSCLC aged ≥65 and diagnosed 2002–2009. We selected patients who received concurrent chemoradiotherapy and determined whether they were (concurrent-consolidation) or were not (concurrent-alone) treated with consolidation chemotherapy. Outcomes were overall and cancer specific survival using a conditional landmark analysis approach.

Results

1688 patients treated with concurrent-alone or concurrent-consolidation were identified with a median follow up of 29 months. Choice of chemotherapy agents did not correlate with outcome. For concurrent-consolidation versus concurrent-alone, the median overall survival was 21 months versus 18 months, respectively (log-rank p = 0.008) and the median cancer specific survival was 23 months versus 19 months, respectively (log-rank p = 0.03). On multivariate analysis, concurrent-consolidation remained associated with improved overall survival (HR 0.85, p = 0.04), and there was a trend for improved cancer specific survival (HR 0.87, p = 0.12). Inverse probability of treatment weighting using propensity scores demonstrated similar findings. Importantly, the benefit of concurrent-consolidation held only for patients treated with carboplatin-taxane but not with cisplatin-etoposide.

Conclusion

Survival outcomes were similar among the five most commonly employed platinum-based doublets. We found that patients receiving cisplatin during radiation do not appear to benefit from additional chemotherapy. However, for patients receiving carboplatin, consolidation chemotherapy was associated with improved overall and cancer specific survival.

Introduction

For locally advanced non-small-cell lung cancer (NSCLC) patients (i.e. stage IIIA/B), combined modality therapy (chemoradiation) is generally recommended [1]. Studies repeatedly demonstrated the benefit of chemotherapy over radiation alone, as well as the benefit of using a platinum-based agent, typically with a second agent, termed “platinum-based doublet therapy” [1], [2], [3]. Chemotherapy can be given in various sequences: before radiation (sequential), during radiation (concurrent-alone), before and during radiation (induction-concurrent), or during and after radiation (concurrent-consolidation). As for radiation therapy, generally treatment is 60–66 Gy in 2 Gy fractions, although hyperfractionated or accelerated courses are also being studied [4].

Controversies remain regarding the optimal choice for the sequence of chemotherapy [1], [5], [6]. Although there are randomized trials showing a lack of efficacy with consolidation after cisplatin-based chemotherapy [7], [8], [9], there are no randomized trials studying consolidation after carboplatin-based chemotherapy. Rather, evidence for consolidation after carboplatin-based chemotherapy has been limited to single-arm trials [10]. Using SEER-Medicare, we studied the use of platinum-based doublet therapies as well as chemoradiation sequences among elderly patients in the US.

Section snippets

Patient selection

Patients diagnosed with NSCLC from January 2002 to December 2009 were identified using Surveillance, Epidemiology, and End Results (SEER)-Medicare. SEER-Medicare is a linked dataset maintained by the National Cancer Institute and contains data from 17 registries accounting for approximately 28% of the US population [11]. The dataset contains demographic, clinical, pathological, outcomes, and Medicare insurance claims data [12]. Follow up was through December 2010.

The cohort included patients

Results

We identified patients with stage III NSCLC diagnosed 2002–2009 who were treated with a platinum-based doublet therapy and radiation (Fig. 1). The five most common chemoradiation regimens were: carboplatin-paclitaxel (1423 patients), cisplatin-etoposide (242 patients), carboplatin-docetaxel (186 patients), carboplatin-etoposide (59 patients), and carboplatin-gemcitabine (33 patients). From 2002 to 2009 cisplatin-etoposide increased from 8% to 17% (Fig. 2). The chemoradiation sequences were:

Discussion

For stage III NSCLC, chemoradiation is the standard treatment for the majority of patients with multi-station or bulky adenopathy. However, no standard chemoradiation regimen or sequence strategy has emerged despite decades of research. We analyzed patients diagnosed 2002–2009 using SEER-Medicare, allowing us to determine the variations in chemoradiation regimens and sequences and perform comparative effectiveness analyses. The most commonly utilized chemotherapy regimens consisted of

Conclusions

In summary, using SEER-Medicare we found that for patients with locally advanced NSCLC undergoing definitive chemoradiation survival outcomes are similar for carboplatin- or cisplatin-containing regimens, as long as consolidation chemotherapy is given for patients receiving carboplatin. Our data therefore support a personalized approach to use of consolidation chemotherapy based on the choice of drugs given during radiation.

Conflict of interest

BWL and MD have received research support from Varian Medical Systems. BWL has received research support from RaySearch Laboratories, and speaking honoraria from Varian Medical Systems. HAW has received research support from Novartis and Eli Lilly. JPH and MIP have no disclosures.

Funding

This work was supported by grants from Varian and the Stanford Society of Physician Scholars. The supporting institutions had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.

Acknowledgements

This study used the linked SEER-Medicare database. The interpretation and reporting of these data are the sole responsibility of the authors. The authors acknowledge the efforts of the Applied Research Program, NCI; the Office of Research, Development and Information, CMS; Information Management Services, Inc.; and the SEER Program tumor registries in the creation of the SEER-Medicare database.

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