THORACIC – Original Submission|Articles in Press

Benefit of adjuvant chemotherapy for resected pathologic N1 non-small cell lung cancer is unrecognized: A subgroup analysis of the JBR10 trial

Published:October 19, 2022DOI:
      Adjuvant chemotherapy is underutilized in clinical practice, in part, because its anticipated survival benefit is limited. We evaluated the impact of AC on overall and recurrence-free survival among completely resected pN1 NSCLC patients enrolled in the North American Intergroup phase III (JBR10) trial. A post-hoc subgroup analysis of pN1 NSCLC patients was performed. Participants were randomized to cisplatin+vinorelbine (AC) (n = 118) or observation (n = 116) following complete resection. The primary endpoint was overall survival (OS). The secondary endpoint was recurrence free survival (RFS). Kaplan-Meier methods were used to compare OS and RFS between the two treatment groups. Cox regression was used to identify factors associated with OS and RFS endpoints. Both groups had similar baseline characteristics. AC patients had improved 5-year OS (AC 61.4% vs observation 41.0%, log-rank p = .008) and 5-year RFS (AC 56.2% vs observation 39.9%, log-rank p = .011) rates compared to observation. Cox regression analyses confirmed the OS (HR 0.583, 95% CI 0.402-0.846, p = .005) and RFS (HR 0.573, 95% CI 0.395-0.830, p = .003) benefit associated with AC. AC was associated with a lower risk (HR 0.648, 95% CI 0.435-0.965, p = .0326) and a lower cumulative incidence (Subdistribution Hazard Ratio [SHR], 0.67, 95% CI 0.449-0.999, p = .0498) of lung cancer deaths. In the JBR10 trial, treatment with AC conferred a significant OS and RFS advantage over observation for pN1 NSCLC patients. These data suggest that pN1 NSCLC patients may experience a disproportionately greater clinical benefit from AC than the 6% survival advantage estimated by the LACE meta-analysis.

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        • Siegel RL
        • Miller KD
        • Fuchs HE
        • et al.
        Cancer statistics, 2022.
        CA Cancer J Clin. 2022; 72: 7-33
        • American Cancer Society
        Cancer Facts & Figures 2022.
        American Cancer Society, Atlanta2022 (Accessed May 12, 2022. Available at:)
        • Ganti AK
        • Klein AB
        • Cotarla I
        • et al.
        Update of incidence, prevalence, survival, and initial treatment in patients with non-small cell lung cancer in the US.
        JAMA Oncol. 2021; 7: 1824-1832
        • Ettinger DS
        • Wood DE
        • Aisner DL
        • et al.
        Non-small cell lung cancer, version 5.2017, NCCN clinical practice guidelines in oncology.
        J Natl Compr Canc Netw. 2017; 15: 504-535
        • Howington JA
        • Blum MG
        • Chang AC
        • et al.
        Treatment of stage I and II non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines.
        Chest. 2013; 143: e278S-e313S
        • Pignon JP
        • Tribodet H
        • Scagliotti GV
        • et al.
        Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group.
        J Clin Oncol. 2008; 26: 3552-3559
        • Toubat O
        • Atay SM
        • Kim AW
        • et al.
        Disparities in guideline-concordant treatment for pathologic N1 non-small cell lung cancer.
        Ann Thorac Surg. 2020; 109: 1512-1520
        • Farrow NE
        • An SJ
        • Speicher PJ
        • et al.
        Disparities in guideline-concordant treatment for node-positive, non-small cell lung cancer following surgery.
        J Thorac Cardiovasc Surg. 2020; 160 (e1): 261-271
        • Bott MJ
        • Patel AP
        • Verma V
        • et al.
        Patterns of care in hilar node-positive (N1) non-small cell lung cancer: A missed treatment opportunity?.
        J Thorac Cardiovasc Surg. 2016; 151 (e2): 1549-1558
        • Kehl KL
        • Zahrieh D
        • Yang P
        • et al.
        Rates of guideline-concordant surgery and adjuvant chemotherapy among patients with early-stage lung cancer in the US ALCHEMIST Study (Alliance A151216).
        JAMA Oncol. 2022; 8: 717-728
        • Douillard JY
        • Tribodet H
        • Aubert D
        • et al.
        Adjuvant cisplatin and vinorelbine for completely resected non-small cell lung cancer: subgroup analysis of the Lung Adjuvant Cisplatin Evaluation.
        J Thorac Oncol. 2010; 5: 220-228
        • Winton T
        • Livingston R
        • Johnson D
        • et al.
        Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer.
        N Engl J Med. 2005; 352: 2589-2597
        • Latouche A
        • Allignol A
        • Beyersmann J
        • et al.
        A competing risks analysis should report results on all cause-specific hazards and cumulative incidence functions.
        J Clin Epidemiol. 2013; 66: 648-653
        • Douillard JY
        • Rosell R
        • De Lena M
        • et al.
        Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomized controlled trial.
        Lancet Oncol. 2006; 7: 719-727
        • White A
        • Kucukak S
        • Lee DN
        • et al.
        Chemotherapy and surgical resection for N1 positive non-small cell lung cancer: better than expected outcomes.
        Semin Thorac Cardiovasc Surg. 2021; 33: 1105-1111
        • National Cancer Institute Surveillance
        Epidemiology, and End Results Program: Cancer Stat Facts Lung and Bronchus Cancer.
        2022 (Accessed May 18, 2022. Available at:)
        • Little AG
        • Gay EG
        • Gaspar LE
        • et al.
        National survey of non-small cell lung cancer in the United States: epidemiology, pathology and patterns of care.
        Lung Cancer. 2007; 57: 253-260
        • Patella M
        • Brunelli A
        • Adams L
        • et al.
        A risk model to predict the delivery of adjuvant chemotherapy following lung resection in patients with pathologically positive lymph nodes.
        Semin Thorac Cardiovasc Surg. 2022; (S1043-0679(22)00051-X)
        • Alam N
        • Shepherd FA
        • Winton T
        • et al.
        Compliance with post-operative adjuvant chemotherapy in non-small cell lung cancer. An analysis of National Cancer Institute of Canada and intergroup trial JBR.10 and a review of the literature.
        Lung Cancer. 2005; 47: 385-394
        • Riquet M
        • Manac'h D
        • Le Pimpec-Barthes F
        • et al.
        Prognostic significance of surgical-pathologic N1 disease in non-small cell carcinoma of the lung.
        Ann Thorac Surg. 1999; 67: 1572-1576
        • Tanaka F
        • Yanagihara K
        • Otake Y
        • et al.
        Prognostic factors in patients with resected pathologic (p-) T1-2N1M0 non-small cell lung cancer (NSCLC).
        Eur J Cardiothorac Surg. 2001; 19: 555-561
        • Demir A
        • Turna A
        • Kocaturk C
        • et al.
        Prognostic significance of surgical-pathologic N1 lymph node involvement in non-small cell lung cancer.
        Ann Thorac Surg. 2009; 87: 1014-1022
        • Mordant P
        • Pricopi C
        • Legras A
        • et al.
        Prognostic factors after surgical resection of N1 non-small cell lung cancer.
        Eur J Surg Oncol. 2015; 41: 696-701
        • Hu F
        • Lin C
        • Chu H
        • et al.
        Prognostic value of different N1 lymph node zones in pN1M0 non-small cell lung cancer: a systematic review and meta-analysis.
        Sci Rep. 2021; 11: 21606
        • Cerfolio RJ
        • Bryant AS
        Predictors of survival and disease-free survival in patients with resected N1 non-small cell lung cancer.
        Ann Thorac Surg. 2007; 84: 182-188
        • Raman V
        • Jawitz OK
        • Yang CJ
        • et al.
        The influence of adjuvant therapy on survival in patients with indeterminate margins following surgery for non-small cell lung cancer.
        J Thorac Cardiovasc Surg. 2020; 159 (e4): 2030-2040
        • Waller D
        • Peake MD
        • Stephens RJ
        • et al.
        Chemotherapy for patients with non-small cell lung cancer: the surgical setting of the Big Lung Trial.
        Eur J Cardiothorac Surg. 2004; 26: 173-182
        • Salazar MC
        • Rosen JE
        • Wang Z
        • et al.
        Association of Delayed Adjuvant Chemotherapy With Survival After Lung Cancer Surgery.
        JAMA Oncol. 2017; 3: 610-619
        • Booth CM
        • Shepherd FA
        • Peng Y
        • et al.
        Adoption of adjuvant chemotherapy for non-small-cell lung cancer: a population-based outcomes study.
        J Clin Oncol. 2010; 28: 3472-3478
        • Wang Z
        • Askamit I
        • Tuscher L
        • et al.
        Rates of guideline adherence among US community oncologists treating NSCLC.
        Am J Manag Care. 2013; 19: 185-192
        • Coleman BK
        • Curtis LH
        • Onaitis MW
        • et al.
        Adjuvant chemotherapy after resection of N1 non-small cell lung cancer: differential impact of new evidence on physician and patient decisions.
        J Thorac Dis. 2015; 7: 243-251
        • Odell DD
        • Feinglass J
        • Engelhardt K
        • et al.
        Evaluation of adherence to the Commission on Cancer lung cancer quality measures.
        J Thorac Cardiovasc Surg. 2019; 157: 1219-1235
        • Ellis RJ
        • Schlick CJR
        • Feinglass J
        • et al.
        Failure to administer recommended chemotherapy: acceptable variation or cancer care quality blind spot?.
        BMJ Qual Saf. 2020; 29: 103-112
        • Wu YL
        • Tsuboi M
        • He J
        • et al.
        Osimertinib in Resected EGFR-Mutated Non-Small-Cell Lung Cancer.
        N Engl J Med. 2020; 383: 1711-1723
        • Wakelee HA
        • Altorki NK
        • Zhou C
        • et al.
        IMpower010: Primary results of a phase III global study of atezolizumab versus best supportive care after adjuvant chemotherapy in resected stage IB-IIIA non-small cell lung cancer (NSCLC).
        J Clin Oncol. 2021; (8500-8500)
        • Aldrighetti CM
        • Niemierko A
        • Van Allen E
        • et al.
        Racial and Ethnic Disparities Among Participants in Precision Oncology Clinical Studies.
        JAMA Netw Open. 2021; 4e2133205

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