Search

Background: The timing of immune checkpoint inhibitor (ICI) administration may influence clinical outcomes in non-small cell lung cancer (NSCLC) patients. Previous studies have shown varying effects of chronotherapy on survival rates, with some suggesting that a higher percentage of doses administered in the morning improves overall survival (OS) and progression-free survival (PFS). This study aimed to evaluate the impact of the timing of the first dose and the percentage of doses administered in the afternoon on survival outcomes in advanced NSCLC patients, as well as explore seasonal variations., Methods: We conducted a retrospective cohort study at a tertiary cancer centre of patients diagnosed with NSCLC and programmed cell death ligand 1 (PD-L1) expression ≥50% who received first-line palliative treatment with pembrolizumab or atezolizumab. Patients were categorized based on the timing of their first dose (before or after 14:30) and further stratified by the percentage of doses received after 14:30. To evaluate seasonal variance, patients were also stratified into two groups: those who received their first dose within three months before or after the winter solstice ("Winter group") and those who received it within three months before or after the summer solstice ("Summer group"). Survival analysis was conducted using the Kaplan-Meier method., Results: We identified 349 patients who met the inclusion criteria. There was no significant difference in PFS or OS between patients receiving their first ICI dose before 14:30 (n=188) and those receiving it after 14:30 (n=161). However, a significant difference in OS was observed in patients who received more than 50% of their doses in the afternoon. Seasonal variations in dosing timing did not significantly impact survival outcomes., Conclusions: Our study suggests that the timing of the first ICI dose does not significantly affect survival outcomes in advanced NSCLC patients. However, patients receiving a higher percentage of their doses in the afternoon may experience poorer OS. Further prospective research is needed to confirm these findings and understand the underlying mechanisms before any changes to clinical practice can be recommended., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-571/coif). I.G.R. has received consulting fees from Janssen. M.P. has received consulting fees from Janssen. R.C. reports grants paid to institution from Roche, AstraZeneca, Pfizer, Clovis, Lilly Oncology, MSD, BMS, Abbvie, Takeda, Janssen, Novartis, and has received consulting fees from AstraZeneca, Boeringher Ingelheim, Lilly Oncology, Roche, Pfizer, MSD, BMS, Takeda, Janssen, Bayer, Novartis, and holds stock or stock options of The Christie Private Care. The other authors have no conflicts of interest to declare., (Copyright © 2025 AME Publishing Company. All rights reserved.)

Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/tlcr-21-634). Dr. IJO has grant from Roche; he also has received consulting fee from Roche, Ono, MSD, Pfizer, Boehringer-Ingelheim, AstraZeneca and Takeda. Dr. YT reports grants from JSPS KAKENHI grant number JP18K15928 and grants from Takeda Science Foundation outside the submitted work. Dr. SW reports grant and personal fee from AstraZeneca and Boehringer Ingelheim, personal fee from Chugai Pharma, Ono Pharmaceutical, Bristol-Myers, Eli Lilly, MSD, Taiho Pharmaceutical, Pfizer, Novartis, Daiichi Sankyo. Dr. RC has received consulting fees, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AZ, MSD, BMS, Roche, TAKEDA, Pfizer, janssen, Bayer, Novartis; Dr. RC has Participation on a Data Safety Monitoring Board or Advisory Board with AZ, MSD, BMS, Roche, TAKEDA, Pfizer, janssen, Bayer, Novartis; Dr. RC has received Support for attending meetings and/or travel from Roche, MSD, Takeda; Dr. RC declares stock ownership with The christie private care. Dr. KM reports medical education grant, Africa from Varian and Pfizer, Clinical trial grant from AstraZeneca and Novartis; travel and accommodations to a clinical trial meeting, 2019 from AstraZeneca; Dr. KM is an unpaid Board of Directors of Global Access to Cancer Care Foundation. Dr. JCS has grant support from National Institute of Health and the Noah’s Hope Foundation; she also has a family member that owns stock options and receives financial compensation from Vida Diagnostics. Dr. MF participated in advisory board for Astrazeneca, AbbVie and Beigene LLC. Dr. DDR reports grants from Bristol-Myers Squibb, grants from AstraZeneca, grants from Boehringer Ingelheim, from Philips, from Olink, from Celgene, from Seattle Genetics, from Roche/Genentech, from Merck/Pfizer, outside the submitted work. Dr. FC reports fees for membership of an advisory board from Roche, AstraZeneca, BMS, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, Pharmamar, Novocure and MSD. Dr NS obtained commercial research grants from Eli Lilly, Chugai Pharmaceutical, Taiho Pharmaceutical, Pfizer Japan, Ono Pharmaceutical, and Nippon Boehringer Ingelheim, and has received speaking honoraria from Eli Lilly, AstraZeneca, MSD Oncology, Chugai Pharmaceutical, Taiho Pharmaceutical, Pfizer Japan, Ono Pharmaceutical, Nippon Boehringer Ingelheim, and Bristol-Myers Squibb Japan. TH serves as an unpaid editorial board member of Translational Lung Cancer Research from Jan 2020 to Dec 2021. FC serves as an unpaid editorial board member of Translational Lung Cancer Research from Aug 2021 to Jul 2023. MF serves as an unpaid editorial board member of Translational Lung Cancer Research from Sep 2019 to Sep 2021. SY serves as an unpaid editorial board member of Translational Lung Cancer Research from Sep 2019 to Sep 2021. GM serves as an unpaid editorial board member of Translational Lung Cancer Research from Aug 2021 to Jul 2023. PH serves as an unpaid editorial board member of Translational Lung Cancer Research from Mar 2021 to Feb 2023. The other authors have no conflicts of interest to declare.

Objective: This review summarizes the current status of neoadjuvant therapy and discusses the choice of new clinical research endpoints for non-small cell lung cancer., Background: Neoadjuvant chemotherapy is a recognized practice in patients with resectable and locally advanced lung cancer. With the introduction of molecular targeted drugs and immune checkpoint inhibitors (ICIs), the overall survival (OS) of patients with lung cancer has been significantly improved, and the original traditional clinical research endpoints are no longer suitable for existing clinical research. In order to accelerate the process of clinical trials and the development and approval of drugs, it is necessary to find suitable alternative indicators as the main indicators of clinical research., Methods: Therefore, this article focuses on clinical trials using disease-free survival (DFS), progression free survival, and pathological evaluation indicators, pathologic complete response and major pathologic response, as surrogate endpoints. We search related literature through PubMed database and clinical trials through clinicaltrials.gov., Conclusions: Pathologic complete response and major pathologic response are recommended as surrogate endpoints in the era of neoadjuvant immunotherapy, and secondary endpoints are listed for the prediction of pathological results. In addition, the definitions of major pathological response (MPR) and PCR should be standardized, and a new pathological evaluation standard should be developed, which is applicable to all current treatment methods., Keywords: Neoadjuvant therapy; resectable lung cancer; clinical research endpoint; pathological response., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr-21-259). Dr. Guibert reports personal fees from Astra Zeneca, Roche, BMS, MSD, AMGEN, Novartis, Pfizer, Chiesi, outside the submitted work. Dr. RC has received honoraria for lectures, presentations, speakers bureaus, educational events and advisory boards from Astrazeneca, Roche, BMS and MSD, and support for attending meetings and/or travel from MSD and Roche, outside the submitted work. The other authors have no conflicts of interest to declare., (2021 Translational Lung Cancer Research. All rights reserved.)

Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr-2020-63). The authors have no conflicts of interest to declare. The authors have no conflicts of interest to declare.

Prognosis of early stage non-small cell lung cancer (eNSCLC) is poor even when treated radically with surgery and (neo)adjuvant chemotherapy (Cht). The discovery of tyrosine kinase inhibitors (TKIs) for oncogene addicted NSCLC and immune checkpoint inhibitors (ICIs) have revolutionised the therapeutic paradigm and improved survival of advanced NSCLC. The unprecedented impact of these drugs has shifted the focus of investigation to early stage disease aiming at improving cure. In this context, several single arm phase II studies evaluating neoadjuvant ICI alone or in combination with platinum-based Cht have shown encouraging rates of pathological response which have spurred several ongoing randomized trials with (neo)adjuvant ICI. More recently, ADAURA study evaluating adjuvant osimertinib demonstrated a profound reduction of the risk of recurrence in patients with stage I (>4 cm)-IIIA eNSCLC harbouring EGFR sensitizing mutations. ICIs and TKIs represent a true revolution in the treatment of eNSCLC call to challenge the current standard of care. However, questions regarding drug resistance, recurrence patterns, biomarker identification, optimal treatment duration and sequencing need be answered to effectively integrate new drugs in the rapidly evolving therapeutic landscape of NSCLC. In this review we critically review new developments and future perspectives of TKIs and ICI as (neo)adjuvant strategies for eNSCLC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr-20-546). The series “Looking for Chimeras in NSCLC: Widen Therapeutic Options Targeting Oncogenic Fusions” was commissioned by the editorial office without any funding or sponsorship. MP serves as an unpaid editorial board member of Translational Lung Cancer Research from Sep 2019 to Sep 2021. Dr. VC reports personal fees from ROCHE, personal fees from BMS, personal fees from ASTRAZENECA, personal fees from BOEHRINGER, personal fees from MSD, outside the submitted work. Dr. MP reports advisory board for BMS, AstraZeneca, Roche and Takeda. Dr. RC reports personal fees from BMS, personal fees from Astrazeneca, personal fees from MSD, personal fees from Roche, outside the submitted work. The authors have no other conflicts of interest to declare., (2020 Translational Lung Cancer Research. All rights reserved.)