Neoadjuvant Targeted Therapy in Resectable NSCLC: Current and Future Perspectives

Lee, Jay M.; McNamee, Ciaran; Toloza, Eric M.; Negrão, Marcelo V.; Lin, Jules; Shum, Elaine; Cummings, Amy L.; Kris, Mark G.; Sepesi, Boris; Bara, Ilze; Kurtsikidze, Nino; Schulze, Katja; Ngiam, Celina; Chaft, Jamie E.

doi:10.1016/j.jtho.2023.07.006

Cited by 26 publications

(10 citation statements)

References 88 publications

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“…The overall survival rate for lung cancer patients is low, with only a 19.7% five-year survival rate [ 3 ]. Its pathological types include small cell lung cancer and non-small cell lung cancer, of which NSCLC accounts for about 80–85% [ 4 ]. With the aging of the population, the acceleration of urban industrialization, and the aggravation of environmental pollution, lung cancer has become a major threat to life and health, with incidence and mortality rates on the rise.…”

Section: Discussionmentioning

confidence: 99%

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Comparison of postoperative complications in mediastinal lymph node dissection versus mediastinal lymph node sampling for early stage non-small cell lung cancer: Protocol for a systematic review and meta-analysis

Chen,

Li,

Cai

et al. 2024

PLoS ONE

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Introduction Lung cancer is the primary cause of cancer-related deaths worldwide, with high rates of morbidity and mortality. The most effective treatment for early stage (I-II) non-small cell lung cancer (NSCLC) is surgical resection. However, the extent of mediastinal lymph nodes removal required and the impact of their removal remains controversial. This systematic review and meta-analysis aimed to evaluate the postoperative complications in patients with stage I-II NSCLC who received mediastinal lymph node dissection (MLND) or mediastinal lymph node sampling (MLNS). Methods and analysis According to the predefined inclusion criteria, we will conduct a comprehensive search for randomized controlled trials (RCTs) and observational studies examining the postoperative complications of MLND compared to MLNS in patients with stage I-II NSCLC. The search will be performed across multiple databases including PubMed, Embase, the Cochrane Library, CNKI, WanFang, Sinomed, VIP, Duxiu, and Web of Science from inception to February 2024. Additionally, relevant literature references will be retrieved and hand searching of pertinent journals will be conducted. Screening, data extraction, and quality assessment will be performed by two independent reviewers. Review Manager 5.4 will be applied in analyzing and synthesizing. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) will be used to assess the quality of evidence for the whole RCTs and used Newcastle-Ottawa scale to assess the methodologic quality of observational studies. Ethics and dissemination This study did not include personal information. Ethical approval was not required for this study. This study is based on a secondary analysis of the literature, so ethical review approval is not required. The final report will be published in a peer-reviewed journal. Conclusion This systematic review will contribute to compare the safety and survival benefits of these two surgical techniques for the treatment of early stage NSCLC, to further guide the selection of surgical approaches. Trial registration The protocol of the systematic review has been registered on Open Science Framework, with a registration number of DOI https://doi.org/10.17605/OSF.IO/N2Y5D.

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Section: Discussionmentioning

confidence: 99%

“…The standard treatment for patients with early stage (I-II) NSCLC is surgery combined with neoadjuvant therapy; nonetheless, metastatic recurrence is still relatively common [ 4 ]. The primary metastatic route of lung cancer is through lymph node metastasis.…”

Section: Introductionmentioning

confidence: 99%

Comparison of postoperative complications in mediastinal lymph node dissection versus mediastinal lymph node sampling for early stage non-small cell lung cancer: Protocol for a systematic review and meta-analysis

Chen,

Li,

Cai

et al. 2024

PLoS ONE

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“…It is crucial to select appropriate high-risk patients and determine the adjuvant therapy required to prevent recurrence in early-stage lung cancer and improve survival. Furthermore, some promising results of neoadjuvant targeted therapy are being reported [49]. Given the high rate of distant metastases after resection in EGFR-mutated NSCLC and the benefit of EGFR-TKIs on survival, it seems important to detect genetic alterations before surgery.…”

Section: Discussionmentioning

confidence: 99%

Genetic Alterations and Risk Factors for Recurrence in Patients with Non-Small Cell Lung Cancer Who Underwent Complete Surgical Resection

Park,

Choi,

Yun

et al. 2023

Cancers

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A definitive surgical resection is the preferred treatment for early-stage non-small cell lung cancer (NSCLC). Research on genetic alterations, including epidermal growth factor receptor (EGFR) mutations, in early-stage NSCLC remains insufficient. We investigated the prevalence of genetic alterations in early-stage NSCLC and the association between EGFR mutations and recurrence after a complete resection. Between January 2019 and December 2021, 659 patients with NSCLC who underwent curative surgical resections at a single regional cancer center in Korea were recruited. We retrospectively compared the clinical and pathological data between the recurrence and non-recurrence groups. Among the 659 enrolled cases, the median age was 65.86 years old and the most common histology was adenocarcinoma (74.5%), followed by squamous cell carcinoma (21.7%). The prevalence of EGFR mutations was 43% (194/451). Among them, L858R point mutations and exon 19 deletions were 52.3% and 42%, respectively. Anaplastic lymphoma kinase (ALK) rearrangement was found in 5.7% of patients (26/453) and ROS proto-oncogene 1 (ROS1) fusion was found in 1.6% (7/441). The recurrence rate for the entire population was 19.7%. In the multivariate analysis, the presence of EGFR mutations (hazard ratio (HR): 2.698; 95% CI: 1.458–4.993; p = 0.002), stage II (HR: 2.614; 95% CI: 1.29–5.295; p = 0.008) or III disease (HR: 9.537; 95% CI: 4.825–18.852; p < 0.001) (vs. stage I disease), and the presence of a pathologic solid type (HR: 2.598; 95% CI: 1.405–4.803; p = 0.002) were associated with recurrence. Among the recurrence group, 86.5% of the patients with EGFR mutations experienced distant metastases compared with only 66.7% of the wild type (p = 0.016), with no significant difference in median disease-free survival (52.21 months vs. not reached; p = 0.983). In conclusion, adjuvant or neoadjuvant targeted therapy could be considered more actively because EGFR mutations were identified as an independent risk factor for recurrence and were associated with systemic recurrence. Further studies on perioperative therapy for other genetic alterations are necessary.

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“…However, the role of adjuvant immunotherapy in resected non-oncogene-addicted NSCLC should be rediscussed, considering also the relevant recent data for the neoadjuvant and perioperative combination of chemotherapy and immunotherapy [26]. On the contrary, the role of targeted agents such as osimertinib and alectinib in a neoadjuvant approach in oncogene-addicted resectable NSCLC is yet to be defined, with phase III trials ongoing [27], and with the adjuvant approach to be considered the only standard of care in the near future.…”

Section: Adjuvant Chemotherapy In the New Era Of Adjuvant Immunotherapymentioning

confidence: 99%

The Role of Adjuvant Chemotherapy before Osimertinib in Epidermal Growth Factor Receptor Mutant Resected Non-Small Cell Lung Cancer and Communicating It to Patients

Maione,

Salvi,

Gridelli

2024

Current Oncology

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Patients with radically resected stage II and III NSCLC are exposed to a high risk of disease recurrence. Thus, adjuvant cisplatin-based chemotherapy is routinely offered to this patient population, although it results in an absolute increase in 5-year survival rate of only 4%. This modest improvement in survival rate makes it challenging to communicate to our patients about the decision to be treated with adjuvant chemotherapy or not. Nowadays, the decision to administer adjuvant chemotherapy or not in resected NSCLC is almost never completely shared with patients because its role is very difficult to explain. The risk–benefit ratio becomes clearly unfavourable in elderly and unfit patients. Recently, the phase III ADAURA trial demonstrated a clinically significant disease-free survival and overall survival benefit with adjuvant osimertinib (with or without adjuvant chemotherapy) versus a placebo in EGFR-mutated stage IB-IIIA resected NSCLC. In this patient population, the decision to administer chemotherapy or not is much more challenging given the great benefit offered by osimertinib alone. Thus, it is time now to improve our communication tools to explain the role of adjuvant chemotherapy to our patients, especially in the EGFR-mutated population, in order to undertake real shared decision making in a clinical context in which the opportunity to administer toxic chemotherapy is debatable and subjective.

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Neoadjuvant Targeted Therapy in Resectable NSCLC: Current and Future Perspectives

Cited by 26 publications

References 88 publications

Comparison of postoperative complications in mediastinal lymph node dissection versus mediastinal lymph node sampling for early stage non-small cell lung cancer: Protocol for a systematic review and meta-analysis

Comparison of postoperative complications in mediastinal lymph node dissection versus mediastinal lymph node sampling for early stage non-small cell lung cancer: Protocol for a systematic review and meta-analysis

Genetic Alterations and Risk Factors for Recurrence in Patients with Non-Small Cell Lung Cancer Who Underwent Complete Surgical Resection

The Role of Adjuvant Chemotherapy before Osimertinib in Epidermal Growth Factor Receptor Mutant Resected Non-Small Cell Lung Cancer and Communicating It to Patients

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