Lack of guideline-concordant treatment for early-stage non-small cell lung cancer common
Click Here to Manage Email Alerts
A substantial proportion of patients with resected early non-small cell lung cancer who consented to an adjuvant therapy screening trial did not receive adequate lymph node dissection or adjuvant chemotherapy, according to study results.
The retrospective cohort study, published in JAMA Oncology, included participants in the Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial (ALCHEMIST) screening study.
“In this cohort, 53% of patients underwent lymph node dissection considered adequate by National Comprehensive Cancer Network guidelines at the time of surgery, and 57% received any adjuvant chemotherapy. We did not observe significant disparities by sociodemographic characteristics in our analysis, although patients with more advanced disease stage were more likely to receive chemotherapy,” Kenneth L. Kehl, MD, MPH, researcher in the division of population sciences in the department of medical oncology at Dana-Farber Cancer Institute and Harvard Medical School, told Healio.
Background and methodology
Kehl and colleagues pursued the study because, despite its use as standard treatment for patients with resectable NSCLC, many patients historically have not received anatomic resection with adequate lymph node dissection and adjuvant chemotherapy.
“At the same time, targeted therapies and immunotherapy are increasingly being studied in the adjuvant setting for NSCLC and are becoming standard options for patients,” Kehl said. “Interpretation of the results of these adjuvant trials of novel therapies could be impacted if trial participants do not always receive guideline-concordant standard treatment.”
Thus, researchers sought to determine the rates guideline-concordant surgery and adjuvant chemotherapy among patients with early-stage NSCLC in the United States.
The analysis included 2,833 patients (mean age, 66.5; standard deviation, 9.2 years; 53% women) with stage IB to stage IIIA NSCLC with tumors of at least 4 cm and/or positive lymph nodes who enrolled in the ALCHEMIST study from Aug. 18, 2014, to April 1, 2019, and did not enroll in a therapeutic adjuvant clinical trial.
Researchers analyzed care patterns overall and according to demographics and clinical factors, such as age, race, ethnicity, education level and geography, among others. They reported five outcomes, including whether patients:
- had anatomic surgical resection;
- had adequate lymph node dissection ( 1 N1 nodal station plus 3 N2 nodal stations);
- received any adjuvant chemotherapy;
- received any cisplatin-based adjuvant chemotherapy; and
- received at least four cycles of adjuvant chemotherapy.
Key findings
Results showed 2,697 patients (95% of the cohort) underwent anatomic surgical resection, 1,513 (53%) had adequate lymph node dissection, 1,617 (57%) received any adjuvant chemotherapy and 1,237 (44%) received at least four cycles of adjuvant platinum-based chemotherapy. Additionally, 965 (34%) received any cisplatin-based adjuvant chemotherapy.
Kehl and colleagues noted similar rates across race and ethnicity.
“The apparent low rates of guideline-concordant therapies was, to some degree, surprising, although rates of adjuvant chemotherapy were similar to those observed in other recent therapeutic trials of novel agents,” Kehl told Healio. “The absence of disparities by sociodemographic characteristics was also somewhat surprising, although this may represent a dynamic in which such disparities may create barriers to enrollment in studies like ALCHEMIST, such that the disparities are less likely to be observed among patients who do enroll.”
Implications
Researchers concluded that efforts are essential to optimize use of proven therapies for early-stage NSCLC and that current adjuvant trial results in this space should be interpreted in light of the potentially suboptimal standard therapy participants receive.
“I think these results illustrate the importance of reporting metrics of guideline-concordant therapy delivery in adjuvant trials of novel agents to aid interpretation,” Kehl said. “At the moment, cytotoxic chemotherapy also remains the only adjuvant systemic therapy modality with a demonstrated overall survival benefit, [and] improved outcomes observed with adjuvant novel agents should not be interpreted as implying that chemotherapy can be omitted for appropriate patients unless clinical trials are specifically designed to investigate the question of that omission.”
The results of the ALCHEMIST screening study also pave the way for future studies examining barriers to widespread adoption of evidence-based treatment guidelines in routine practices, Chee Khoon Lee, MBBS, MMedSci, MBiostat, PhD, and Monica Tang, MBBS, MMed, both of Centre for Big Data Research in Health at University of New South Wales in Australia, wrote is an accompanying editorial.
“When real-world evidence does not support the use of existing treatments, such as extensive nodal dissection or cisplatin-based chemotherapy for older patients with poor performance status, additional prospective clinical trial evidence will be needed to investigate more appropriate treatment strategies for these patient populations,” they wrote. “If variations in the rates of guideline-recommended practice are attributable to health system or sociodemographic factors, then addressing these system-level barriers will be critical for promoting equitable cancer care and improving outcomes for all patients with early-stage NSCLC.”
References:
Kehl KL, et al. JAMA Oncol. 2022;doi: 10.1001/jamaoncol.2022.0039.
Tang M, et al. JAMA Oncol. 2022;doi:10.1001/jamaoncol.2022.0038.
For more information:
Kenneth L. Kehl, MD, MPH, can be reached at Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215; email: kenneth_kehl@dfci.harvard.edu.
Perspective
Back to Top
Khaled Hassan, MD
Surgical resection remains the cornerstone of treatment for patients with medically operable early-stage lung cancer. Multiple studies and meta-analyses showed the significant role of adjuvant chemotherapy in improving OS. Thus, four cycles of platinum based (cisplatin preferred) chemotherapy doublet usually is recommended for patients with stage IIA to stage IIIA disease.
In this manuscript, the authors used a cohort of patients from ALCHEMIST to determine the level of adherence to these recommendations. The authors reported that 53% of patients underwent appropriate lymph node dissection and only 57% received adjuvant chemotherapy, with 44% receiving four cycles of platinum-based therapy. These findings highlight the discordance between validated management protocols based on phase 3 clinical trial evidence and the applied real-world practice.
Of interest, this discrepancy is not due to lack of access to care secondary to a socioeconomic barrier; on the contrary, this is a highly selective population already enrolled in a screening clinical trial.
Clearly, we have a multifaceted challenge in clinical trial design, caregivers’ implementation of guidelines, and patients’ acceptance of and adherence to treatment regimens. Are the requirements set in clinical trials not translatable to real life? If so, should clinical trial design approach change to mirror what is practically doable? Should there be educational material, training workshops and update courses required for caregivers to attend? Should cases be referred to highly specialized tertiary centers for such complex care? Should implementation of new guidelines be associated with public awareness campaigns or easy access information database for better patient education?
Based on this manuscript, our challenge is not only to overcome socioeconomic barriers to health care but also to provide the appropriate standard of care to all, which might prove to be more difficult.
Collapse
Click Here to Manage Email Alerts