Rates of Guideline-Concordant Surgery and Adjuvant Chemotherapy Among Patients With Early-Stage Lung Cancer in the US ALCHEMIST Study (Alliance A151216)

Abstract

Importance: Standard treatment for resectable non-small cell lung cancer (NSCLC) includes anatomic resection with adequate lymph node dissection and adjuvant chemotherapy for appropriate patients. Historically, many patients with early-stage NSCLC have not received such treatment, which may affect the interpretation of the results of adjuvant therapy trials.

Objective: To ascertain patterns of guideline-concordant treatment among patients enrolled in a US-wide screening protocol for adjuvant treatment trials for resected NSCLC.

Design, setting, and participants: This retrospective cohort study included 2833 patients with stage IB to IIIA NSCLC (per American Joint Committee on Cancer 7th edition criteria) who enrolled in the Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial (ALCHEMIST) screening study (Alliance for Clinical Trials in Oncology A151216) from August 18, 2014, to April 1, 2019, and who did not enroll in a therapeutic adjuvant clinical trial; patients had tumors of at least 4 cm and/or with positive lymph nodes. Statistical analysis was conducted from June 1, 2020, through October 1, 2021.

Exposures: Care patterns were ascertained overall and by sociodemographic and clinical factors, including age, sex, race and ethnicity, educational level, marital status, geography, histologic characteristics, stage, genomic variant status, smoking history, and comorbidities.

Main outcomes and measures: Five outcomes are reported: whether patients (1) had anatomic surgical resection, (2) had adequate lymph node dissection (≥1 N1 nodal station plus ≥3 N2 nodal stations), (3) received any adjuvant chemotherapy, (4) received any cisplatin-based adjuvant chemotherapy, and (5) received at least 4 cycles of adjuvant chemotherapy.

Results: Of the 2833 patients (1505 women [53%]; mean [SD] age, 66.5 [9.2] years) included in this analysis, 2697 (95%) had anatomic surgical resection, 1513 (53%) had adequate lymph node dissection, 1617 (57%) received any adjuvant chemotherapy, 1237 (44%) received at least 4 cycles of adjuvant platinum-based chemotherapy, and 965 (34%) received any cisplatin-based adjuvant chemotherapy. Rates were similar across race and ethnicity.

Conclusions and relevance: This cohort study found that among participants in a screening protocol for adjuvant clinical trials for resected early-stage NSCLC, just 53% underwent adequate lymph node dissection, and 57% received adjuvant chemotherapy, despite indications for such treatment. These results may affect the interpretation of adjuvant trials. Efforts are needed to optimize the use of proven therapies for early-stage NSCLC.

Trial registration: ClinicalTrials.gov Identifier: NCT02194738.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Kehl reported receiving personal fees from Aetion; grants from IBM; and honoraria from Roche outside the submitted work. Dr Sands reported receiving personal fees from AstraZeneca, Pharma Mar, Jazz Pharmaceuticals, Boehringer Ingelheim, Lilly, Medtronic, Takeda, Blueprint Medicines, Loxo, Foundation Medicine, Guardant, and Daiichi-Sankyo outside the submitted work. Dr Oxnard reported receiving personal fees from Foundation Medicine and Roche outside the submitted work. Dr Gillaspie reported receiving personal fees from Intuitive Surgical, AstraZeneca, and the American Society of Clinical Oncology outside the submitted work. Dr Ramalingam reported receiving grants to institution from Amgen, AstraZeneca, Bristol Myers Squibb, Merck, Takeda, Pfizer, and GlaxoSmithKline; and personal fees from Amgen, GlaxoSmithKline, AstraZeneca, Bristol Myers Squibb, Lilly, Eisai, Takeda, Merck outside the submitted work. Dr Govindan reported receiving honoraria for consulting from Achilles Therapeutic, GenePlus, Inivata, and Merck; and being a principal investigator or co-investigator on industry-sponsored clinical trials for which their institution receives funding and research support. Dr Osarogiagbon reported receiving grants from the National Cancer Institute during the conduct of the study; grants from the National Cancer Institute; personal fees from the National Cancer Institute, the American Cancer Society, Association of Community Cancer Centers, AstraZeneca, Eli Lilly, Biodesix, Genentech/Roche, Lungevity Foundation, National Cancer Institute, and Tryptych Healthcare Partners; stock ownership in Eli Lilly, Gilead Sciences, and Pfizer; serving as board chair for SWOG Hope Foundation for Cancer Research; and having a patent for lymph node specimen collection kit issued in China and Germany and US patents for a lung cancer specimen kit outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. Cohort Derivation

ALCHEMIST indicates Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial. aExcluded 6 patients registered in error (4 duplicates; 2 died prior to registration).

Figure 2.. Adjusted Associations of Patient Characteristics With Adequate Lymph Node Dissection

Estimates derived from multivariable modified Poisson regression models with multiple imputation applied to missing data for covariates. COPD indicates chronic obstructive pulmonary disease; GED, General Educational Development Certification; LAPS, Lead Academic Performance Site; NSCLC, non–small cell lung cancer; and Q, quintile.

Figure 3.. Adjusted Associations of Patient Characteristics With Any Adjuvant Chemotherapy

Estimates derived from multivariable modified Poisson regression models with multiple imputation applied to missing data for covariates. COPD indicates chronic obstructive pulmonary disease; GED, General Educational Development Certification; LAPS, Lead Academic Performance Site; NSCLC, non–small cell lung cancer; and Q, quintile. aSignificant at Bonferroni-corrected P < .00024.