Characteristics of toxicity occurrence patterns in concurrent chemoradiotherapy after induction chemotherapy for patients with locally advanced non-small cell lung cancer: a pooled analysis based on individual patient data of CALGB/Alliance trials

Lexie Zidanyue Yang; Qihua He; Jianrong Zhang; Apar Kishor Ganti; Thomas E Stinchcombe; Herbert Pang; Xiaofei Wang

doi:10.21037/tcr-22-2006

Characteristics of toxicity occurrence patterns in concurrent chemoradiotherapy after induction chemotherapy for patients with locally advanced non-small cell lung cancer: a pooled analysis based on individual patient data of CALGB/Alliance trials

Transl Cancer Res. 2022 Oct;11(10):3506-3521. doi: 10.21037/tcr-22-2006.

Authors

Lexie Zidanyue Yang^#¹, Qihua He^#², Jianrong Zhang^#^{1

3

4

5}, Apar Kishor Ganti⁶, Thomas E Stinchcombe⁷, Herbert Pang¹, Xiaofei Wang^{1

8}

Affiliations

¹ Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC, USA.
² Department of Oncology, the First Affiliated Hospital of Guangzhou Medical University, China State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou, China.
³ Brown School at Washington University in St. Louis, St. Louis, MO, USA.
⁴ Melboune Medical School & Centre for Cancer Research, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia.
⁵ Victorian Comprehensive Cancer Centre, Melbourne, Victoria, Australia.
⁶ Department of Internal Medicine, VA Nebraska Western Iowa Healthcare System and University of Nebraska Medical Center, Omaha, NE, USA.
⁷ Department of Medicine, Duke University School of Medicine, Durham, NC, USA.
⁸ Alliance Statistics and Data Management Center, Duke University, Durham, NC, USA.

^# Contributed equally.

Abstract

Background: For patients with locally advanced non-small cell lung cancer (NSCLC), concurrent chemoradiotherapy is the foundational treatment strategy. Adding induction chemotherapy did not achieve a superior efficacy but increased the burden from toxicity. Accordingly, we retrospectively investigated the toxicity patterns through pooling individual patient data of the Cancer and Leukemia Group B (CALGB)/Alliance trials.

Methods: We included a total of 637 patients with unresectable stage III NSCLC who received induction chemotherapy with a platinum doublet and concurrent chemoradiotherapy and experienced at least one adverse event (AE) in CALGB 9130, 9431, 9534, 30105, 30106 and 39801 trials. The following toxicity occurrence patterns were evaluated: top 10 most frequent AEs, AE distribution by grade, rate of treatment discontinuation due to AEs, associations of AE occurrence with patient characteristics and treatment phase, the time to the first grade ≥3 AE occurrence and its associations with patient characteristics and treatment phase.

Results: The occurrence of AEs was the main reason accounting for treatment discontinuation (60 of 637 among all patients; 18 of 112 patients who experienced the induction phase only; 42 of 525 patients who experienced both phases). All patients experienced a total of 11,786 AEs (grade ≥3: 1,049 of 5,538 in induction phase, 1,382 of 6,248 in concurrent phase). Lymphocytes and white blood count were of top 3 grade ≥3 AEs that patients experienced the most in the either phase. Multivariable analysis found AE occurrence was associated with age ≥65 [any grade: odds ratio (OR) =1.44, 95% confidence interval (CI): 1.12-1.86] and the concurrent phase (grade ≥3: OR =1.86, 95% CI: 1.41-2.47; any grade: OR =1.47, 95% CI: 1.19-1.81). Patients in the concurrent phase were more likely and earlier to develop grade ≥3 AEs than those in the induction phase [hazard ratio (HR) =4.37, 95% CI: 2.52-7.59].

Conclusions: The report provides a better understanding regarding the toxicity occurrence patterns in concurrent chemoradiotherapy after induction chemotherapy.

Keywords: Lung neoplasms; adverse effects; chemoradiotherapy.