[Progress in Neoadjuvant Immunotherapies for Resectable Non-small Cell Lung Cancer].
Wang Shuaibo,Mao Yousheng
Zhongguo fei ai za zhi = Chinese journal of lung cancer
Resectable non-small cell lung cancer (NSCLC) is currently considered as a potentially curable disease. Surgery is still the main treatment mode for resectable NSCLC, but quite a few patients will have local recurrence and distant metastasis after surgery. Therefore, preoperative and postoperative adjuvant therapy may be necessary in order to improve the long term outcome. Immunocheckpoint inhibitor has been demonstrated clinically to be effective andapproved as first- or second-line treatment agent in metastatic NSCLC or partially locally advanced NSCLC. The remarkable efficacy of immunotherapy for advanced lung cancer has attracted more and more attention from the researchers to the role of immunotherapy as neoadjuvent therapy in resectable non-small cell lung cancer. This article systematically reviewed the clinical trials of neoadjuvant immunotherapy for resectable NSCLC before surgery.
Striving toward Improved Outcomes for Surgically Resectable Non-Small Cell Lung Cancer: the Promise and Challenges of Neoadjuvant Immunotherapy.
Gentzler Ryan D,Riley David O,Martin Linda W
Current oncology reports
PURPOSE OF REVIEW:Immunotherapy has revolutionized the treatment of non-surgical stage III and stage IV non-small cell lung cancer (NSCLC). Here, we review emerging data on the safety, feasibility, and efficacy of neoadjuvant immunotherapy in the setting of earlier stage surgically resectable lung cancer. RECENT FINDINGS:Several small studies support the safety and feasibility of neoadjuvant immunotherapy, noting similar perioperative rates of morbidity and mortality compared with historical controls. Data from several phase II trials have shown high rates of major pathologic response (MPR), though it is unclear if this will correlate with a survival benefit. Phase III trials of neoadjuvant immunotherapy alone or in combination with chemotherapy are ongoing. Neoadjuvant immunotherapy offers a promising treatment modality in earlier stage NSCLC patients. Results of ongoing phase II and phase III trials will be essential in determining how to best integrate this treatment modality in the future.
Neoadjuvant and Adjuvant Immunotherapy: Opening New Horizons for Patients With Early-Stage Non-small Cell Lung Cancer.
Bai Rilan,Li Lingyu,Chen Xiao,Chen Naifei,Song Wei,Cui Jiuwei
Frontiers in oncology
Lung cancer is the most common malignant tumor with the highest mortality, and about 84% are non-small cell lung cancer (NSCLC). However, only a small proportion of patients with newly diagnosed lung tumors can receive curative surgery and have a high risk of postoperative recurrence. At present, there are many perioperative treatment methods being continuously explored, such as chemotherapy and targeted therapy, continuously enriching the content of neoadjuvant and adjuvant therapy in early-stage NSCLC. But disappointingly, for patients with driver gene mutation, the significant disease-free survival (DFS) benefit of targeted drugs failed to translate into overall survival (OS) benefit, and for negative patients, chemotherapy has reached a plateau in improving efficacy and survival. Immunotherapy represented by immune checkpoint inhibitors (ICIs) has been researched in more and more clinical trials in patients with early-stage operable disease, gradually enriching the existing treatments. This review focuses on the research progress of clinical trials of neoadjuvant and adjuvant therapy with ICIs in early-stage NSCLC, the exploration of response evaluation and predictive biomarkers, and the urgent problems to be solved in the future.
Treatment of stage III non-small cell lung cancer in the era of immunotherapy: pathological complete response to neoadjuvant pembrolizumab and chemotherapy.
Yang Zhang-Ru,Liu Mi-Na,Yu Jia-Hua,Yang Yun-Hai,Chen Tian-Xiang,Han Yu-Chen,Zhu Lei,Zhao Ji-Kai,Fu Xiao-Long,Cai Xu-Wei
Translational lung cancer research
Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancers. The expected 5-year survival of stage III NSCLC ranges from 13% to 36% for stage III. Due to the heterogeneity and poor efficacy of stage III patients, there is great controversy on how to optimize the therapy strategy. Immunotherapy is providing better clinical efficacy to more NSCLC patients, and is rapidly extending its range of care from advanced stage to locally advanced stage and early stage NSCLC. Due to the patient's strong treatment intention, drug availability, and a few encouraging results from clinical trials (NADIM, NCT02716038, etc.), the authors observed a case of stage III NSCLC that achieved complete remission after receiving neoadjuvant chemotherapy combined with immunotherapy. In view of such a satisfactory result in neoadjuvant therapy, this article discusses how comprehensive treatment for stage III NSCLC patients may be conducted and the manner in which various therapeutic techniques can be mastered in the era of immunotherapy. Immunotherapy has opened the exploratory space for finding resolutions to numerous challenges of treating stage III NSCLC. Further clinical studies and exploration of personalized treatment, guided by imaging data, and clinical and pathological biomarkers are imperative for the benefit of these patients.
Controversies and challenges in the pathologic examination of lung resection specimens after neoadjuvant treatment.
Weissferdt Annikka,Pataer Apar,Swisher Stephen G,Heymach John V,Gibbons Don L,Cascone Tina,Sepesi Boris
Lung cancer (Amsterdam, Netherlands)
New therapy approaches in the treatment of surgically resectable non-small cell lung cancer (NSCLC) challenge the traditional handling and examination of pathology specimens. The increasingly common use of neoadjuvant therapies before surgical resection, due to advantages in novel drug administration, tolerance, and measurement of radiographic and pathologic response compared to adjuvant treatment, has the potential to alter the microscopic tumor appearance and its biology. Currently, many clinical trials use pathologic response as a surrogate endpoint of clinical efficacy, since the extent of residual viable tumor appears to correlate with outcome in patients treated with neoadjuvant chemotherapy. Consequently, pathologic assessment of the extent of residual viable tumor is of paramount importance. However, high level evidence-based guidelines on how to process and evaluate such specimens are lacking. Moreover, while pathologic response has been shown to be associated with survival after chemotherapy, its significance after immunotherapy remains to be determined. Additionally, many clinical trials do not routinely include pathologists in trial design, which may lead to non-standardized evaluation of pathologic response. Although recently, several algorithms have been proposed to address these issues, none of them represents evidence-based recommendations or is universally applied. Therefore, controversies and challenges continue to exist, raising concerns about the validity, reproducibility, and comparability of the results of many neoadjuvant clinical trials. Herein, we discuss the current difficulties in pathologic specimen evaluation following neoadjuvant therapy in NSCLC and propose potential approaches to overcome these challenges.
Neoadjuvant immunotherapy for non-small cell lung cancer: State of the art.
Kang Jin,Zhang Chao,Zhong Wen-Zhao
Cancer communications (London, England)
Lung cancer mortality has decreased over the past decade and can be partly attributed to advances in targeted therapy and immunotherapy. Immune checkpoint inhibitors (ICIs) have rapidly evolved from investigational drugs to standard of care for the treatment of metastatic non-small cell lung cancer (NSCLC). In particular, antibodies that block inhibitory immune checkpoints, such as programmed cell death protein 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1), have revolutionized the treatment of advanced NSCLC, when administered alone or in combination with chemotherapy. Immunotherapy is associated with higher response rates, improved overall survival (OS), and increased tolerability compared with conventional cytotoxic chemotherapy. These benefits may increase the utility of immunotherapy and its combinational use with chemotherapy in the neoadjuvant treatment of patients with NSCLC. Early findings from various ongoing clinical trials suggest that neoadjuvant ICIs alone or combined with chemotherapy may significantly reduce systemic recurrence and improve long-term OS or cure rates in resectable NSCLC. Here we further summarize the safety and efficacy of various neoadjuvant treatment regimens including immunotherapy from ongoing clinical trials and elaborate the role of neoadjuvant immunotherapy in patients with resectable NSCLC. In addition, we discuss several unresolved challenges, including the evaluations to assess neoadjuvant immunotherapy response, the role of adjuvant treatment after neoadjuvant immunotherapy, the efficacy of treatment for oncogenic-addicted tumors, and predictive biomarkers. We also provide our perspective on ways to overcome current obstacles and establish neoadjuvant immunotherapy as a standard of care.