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The objective of this study was to reveal the effectiveness of repetitive transcranial magnetic stimulation (rTMS) for Japanese patients with treatment-resistant depression (TRD) in clinical practice, based on real-world data from a nationwide multicenter observational study in Japan. Clinical data of patients with TRD treated with rTMS (NeuroStar TMS treatment system) under public insurance coverage were retrospectively collected from 21 institutes nationwide between June 2019 and December 2023. Depression severity was assessed by the 17-item Hamilton Depression Rating Scale (HAMD-17). Response and remission were defined as ≥50 % reduction from baseline and ≤7 points on the HAMD-17, respectively. The primary outcome was the changes in the HAMD-17 score from baseline to the endpoint following rTMS. Data from 497 patients with TRD were candidates for this study. The HAMD-17 scores (mean (SD)) improved significantly from 18.9 (5.3) to 9.7 (6.6), respectively. The response and remission rates at the end of rTMS therapy as assessed by the HAMD-17 were 53.5 % and 42.8 %, respectively. The dropout rate due to adverse effects was 4.2 %, and the treatment was generally well tolerated. No convulsive seizures or manic changes were observed. These results indicate that conventional rTMS is effective and safe in Japanese patients with TRD., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest in relation to this study., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: Predicting the prognosis of lung cancer is crucial for providing optimal medical care. However, a method to accurately predict the overall prognosis in patients with stage IV lung cancer, even with the use of machine learning, has not been established. Moreover, the inter-institutional generalizability of such algorithms remains unexplored. This study aimed to establish machine learning-based algorithms with inter-institutional generalizability to predict prognosis., Materials and Methods: This multicenter, retrospective, hospital-based cohort study included consecutive patients with stage IV lung cancer who were randomly categorized into the training and independent test cohorts with a 2:1 ratio, respectively. The primary metric to assess algorithm performance was the area under the receiver operating characteristic curve in the independent test cohort. To assess the inter-institutional generalizability of the algorithms, we investigated their ability to predict patient outcomes in the remaining facility after being trained using data from 15 other facilities., Results: Overall, 6,751 patients (median age, 70 years) were enrolled, and 1,515 (22 %) showed mutated epidermal growth factor receptor expression. The median overall survival was 16.6 (95 % confidence interval, 15.9-17.5) months. Algorithm performance metrics in the test cohort showed that the areas under the curves were 0.90 (95 % confidence interval, 0.88-0.91), 0.85 (0.84-0.87), 0.83 (0.81-0.85), and 0.85 (0.82-0.87) at 180, 360, 720, and 1,080 predicted survival days, respectively. The performance test of 16 algorithms for investigating inter-institutional generalizability showed median areas under the curves of 0.87 (range, 0.84-0.92), 0.84 (0.78-0.88), 0.84 (0.76-0.89), and 0.84 (0.75-0.90) at 180, 360, 720, and 1,080 days, respectively., Conclusion: This study developed machine learning algorithms that could accurately predict the prognosis in patients with stage IV lung cancer with high inter-institutional generalizability. This can enhance the accuracy of prognosis prediction and support informed and shared decision-making in clinical settings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Daichi Fujimoto reported receiving grants and personal fees from AstraZeneca KK and Boehringer Ingelheim Japan Inc. and personal fees from Ono Pharmaceutical Co., Ltd., Bristol-Myers Squibb Co., Ltd., Takeda Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., MSD KK, Eli Lilly Japan K.K., Kyowa Kirin, Daiichi Sankyo, and Novartis Pharma KK outside the submitted work. Hidetoshi Hayashi reported receiving grants from PAREXEL International Corp., Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., MSD K.K., Ono Pharmaceutical Co., Ltd., SYNEOS HEALTH CLINICAL K.K., Covance Japan Inc., Sanofi K.K., Novartis Pharma K.K., Bristol Myers Squibb Company, Janssen Pharmaceutical K.K., Eisai Co., Ltd., Japan Clinical Research Operations, AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., Sysmex Corporation, Takeda Pharmaceutical Co., Ltd., IQVIA Services JAPAN K.K., GlaxoSmithKline K.K., EPS Corporation, Medical Research Support, PRA Health Science, Inc., Eisai., Inc., Nippon Boehringer Ingelheim Co., Ltd., and PPD-SNBL K.K. and personal fees from AstraZeneca K.K., Bristol Myers Squibb Company, Amgen, Inc., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Ono Pharmaceutical Co., Ltd., and Pfizer Japan Inc outside the submitted work. Yukihiro Toi reported receiving personal fees from Bristol-Myers Squibb Company, Ono Pharmaceutical Co., Ltd., MSD K.K., AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Pfizer, Inc., and Kyowa Kirin Co., Ltd., outside the submitted work. Toshihide Yokoyama reported receiving personal fees from AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Pfizer Japan Inc, Bristol-Myers Squibb Co., Ltd., Ono Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd., MSD, Novartis, and Merck Biopharma Co., Ltd. outside the submitted work. Terufumi Kato reported receiving grants from Abbvie, Amgen, AstraZeneca, BeiGene, BluePrint, Chugai, Daiichi-Sankyo, Eli Lilly, Haihe, Merck KGaA, MSD, Novartis, Pfizer, Regeneron, Takeda, and TurningPoint and personal fees from Amgen, AstraZeneca, BeiGene, Boehringer Ingelheim, Chugai, Daiichi-Sankyo, Eli Lilly, GlaxoSmithKline, Janssen, Merck KGaA, MSD, Novartis, Ono, Pfizer, Taiho, and Takeda outside the submitted work, and his wife is an employee of Eli Lilly. Teppei Yamaguchi reported receiving personal fees from Ono Pharmaceutical, Chugai Pharmaceutical, Eli Lilly, Taiho Pharmaceutical, AstraZeneca, MSD, Bristol-Meyers Squibb, and Novartis outside the submitted work. Kaoru Tanaka reported receiving personal fees from AstraZeneca, Merck Biopharma, Eisai, Bristol-Myers Squibb, Ono Pharmaceutical, MSD, Chugai Pharmaceutical, Takeda Pharmaceutical Co., Ltd., Taiho Pharmaceutical, and Novartis Pharma outside the submitted work. Satoru Miura reported receiving personal fees from AstraZeneca KK, Ono Pharmaceutical Co., Ltd., Bristol-Myers Squibb Co., Ltd., Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., MSD K.K., Boehringer Ingelheim Japan Inc, Eli Lilly Japan K.K., Novartis Pharma K.K., Pfizer, Kyowa Hakko Kirin, Daiichi Sankyo, Abbive, Nippon Kayaku, AMGEN, Merck, and Takeda Pharmaceutical Co., Ltd. outside the submitted work. Motohiro Tamiya reported receiving personal fees from Pfizer, Chugai Pharmaceutical, Ono Pharmaceutical, MSD, Boehringer Ingelheim, AstraZeneca, Taiho Pharmaceutical, Eli Lilly, Bristol-Myers Squibb, and Amgen outside the submitted work. Motoko Tachihara reported receiving grants and personal fees from AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., and Eli Lilly Japan Co., Ltd., and personal fees from Ono Pharmaceutical Co., Ltd., Bristol-Myers Squibb Co., Ltd., MSD K.K., Novartis pharmaceuticals K.K., Takeda Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Daiichi Sankyo, Pfizer Japan, Inc., and Janssen Pharmaceutical K.K. Takehito Shukuya reported receiving grants and personal fees from AstraZeneca, Chugai Pharmaceutical, Boehringer Ingelheim, Novartis, and MSD and personal fees from Taiho Pharma, Daiichi-Sankyo, Ono Pharmaceutical, Bristol-Myers Squibb, Nippon Kayaku, Pfizer, Takeda Pharmaceutical Co., Ltd., and Eli Lilly outside the submitted work. Yuko Tsuchiya-Kawano reported receiving personal fees from Bristol-Myers Squibb, Taiho Pharmaceutical, Chugai Pharmaceutical, AstraZeneca, Kyowa Hakko Kirin, MSD, and Ono Pharmaceutical outside the submitted work. Yuki Sato reported receiving personal fees from AstraZeneca, MSD, Novartis, Chugai Pharmaceutical, Ono Pharmaceutical, Pfizer, Taiho Pharmaceutical, Nippon Kayaku, Bristol Myers Squibb, Eli Lilly, Takeda Pharmaceutical Co., Ltd., Kyowa Kirin, and Boehringer Ingelheim outside the submitted work. Satoshi Ikeda reported receiving personal fees from AstraZeneca, Bristol Myers Squibb, Ono Pharmaceutical, Chugai Pharmaceutical, Taiho Pharmaceutical, Boehringer Ingelheim, Eli Lilly, Takeda Pharmaceutical Co., Ltd., Daiichi-Sankyo, and Pfizer outside the submitted work. Shinya Sakata reported receiving personal fees from AstraZeneca, Chugai Pharmaceutical Co., Ltd., Taiho Pharmaceutical, and Takeda Pharmaceutical outside the submitted work. Takeshi Masuda reported receiving personal fees from MSD K.K., Eli Lilly Japan K.K., Chugai Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., AstraZeneca K.K., Ono Pharmaceutical Co., Ltd., Bristol-Myers Squibb Co., Ltd., and Kyowa Kirin outside the submitted work. Isamu Okamoto reported receiving personal fees from Nippon Boehringer Ingelheim Co., Ltd., AstraZeneca Plc., Eli Lilly Japan K.K., Takeda Pharmaceutical Co., Ltd., and Novartis Pharma K.K. outside the submitted work. Nobuyuki Yamamoto reported receiving grants from AstraZeneca K.K., MSD K.K., Amgen Astellas BioPharma, Eisai Co., Ltd., Sanofi K.K., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Novartis Pharma K.K., Janssen Pharmaceutical K.K., Amgen K.K., Taiho Pharmaceutical Co., Ltd., Toppan USA, Inc., Nippon Boehringer Ingelheim Co., Ltd., and Daiichi Sankyo Co., Ltd. and personal fees from MSD K.K., Amgen K.K., Takeda Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Nippon Boehringer Ingelheim Co., Ltd., AstraZeneca K.K., Ono Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Novartis Pharma K.K., and Merck Biopharma Co., Ltd., outside the submitted work. The remaining authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The expansion of preoperative immunochemotherapy has led to an increase in the number of patients with lung cancer receiving immune checkpoint inhibitors (ICIs). Therefore, oncologists should manage a variety of immune-related adverse events (irAEs). One of the rare, life-threatening, and recently proposed irAEs is cytokine release syndrome (CRS). Although the standard treatment of irAE is systemic administration of steroids, it has been suggested that tocilizumab may be an effective treatment option for CRS., Case: This case describes a 69-year-old man with stage IIIA lung adenocarcinoma who received chemotherapy and nivolumab, which is an ICI, as neoadjuvant immunochemotherapy. After the first administration, the patient developed severe skin rash, fever, and arthralgia. We suspected irAEs and administered systemic steroids. However, fever and arthralgia did not improve, although the skin rash disappeared. These were also significant challenges for surgery. Noting the elevated levels of inflammatory cytokines, we consulted a rheumatologist. Finally, we decided to terminate neoadjuvant therapy after one cycle and administer tocilizumab. Tocilizumab dramatically improved the patient's symptoms and allowed him to undergo radical surgery. Pathological findings revealed that the patient achieved a major pathological response., Conclusion: This indicates the potential effectiveness of early tocilizumab administration for ICI-induced CRS, even in mild cases., (© 2024 The Author(s). Cancer Reports published by Wiley Periodicals LLC.)

This study registered consecutive cases to elucidate the efficacy of rTMS treatment for depression within the Japanese public health insurance system. Of the 102 patients with depression who received rTMS over the left dorsolateral prefrontal cortex, 44 (43.1 %) patients reached remission and 14 (13.7 %) patients did not reach remission but responded to treatment. No serious adverse events occurred. Low baseline HAMD-17 score was associated with remission after rTMS treatment. Favorable outcomes of rTMS treatment were shown in this cohort within the Japanese public insurance system. Our results provide insights into rTMS treatment for depression in real-world clinical setting., Competing Interests: Declaration of Competing Interest Authors Imazu, Ikeda, Shinosaki, and Takahashi have received speaker honoraria from Teijin Pharma Limited. Author Kanazawa has received materials supervision fee from Teijin Pharma Limited., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: As first-line treatment for stage IV or recurrent non-small cell lung cancer, combination immunotherapy with nivolumab and ipilimumab, with or without chemotherapy, had demonstrated survival benefits over chemotherapy; however, data on Japanese patients are limited., Methods: LIGHT-NING was a multicenter, observational study and retrospectively collected data. In this interim analysis, we analyzed patients who received combination immunotherapy between 27 November 2020 and 31 August 2021 for the treatment status, safety objectives (treatment-related adverse events and immune-related adverse events incidences), and effectiveness objectives (objective response rate and progression-free survival) to determine the characteristics and early safety information., Results: We analyzed 353 patients, with a median follow-up of 7.1 (interquartile range, 5.0-9.7) months. Overall, 60.1 and 39.9% received nivolumab plus ipilimumab with and without chemotherapy, respectively. In these cohorts, the median age was 67 and 72 years; 10.8 and 35.5% were aged ≥75 years; 80.2 and 79.4% were male; 5.2 and 13.5% had a performance score ≥ 2; 32.1 and 27.0% developed grade 3-4 immune-related adverse events; treatment-related deaths were observed in 6 (2.8%) and 5 (3.5%) patients, respectively. Grade 3-4 immune-related adverse event incidence was the highest within the first month of treatment in both cohorts, although the immune-related adverse event risk persisted throughout. No new safety signals were observed at this interim analysis. The median progression-free survival was 6.0 (95% confidence interval, 5.2-7.6) and 5.8 (4.3-7.0) months in nivolumab plus ipilimumab with and without chemotherapy cohorts, respectively., Conclusions: LIGHT-NING offers valuable insights into combination immunotherapy for untreated patients with stage IV or recurrent non-small cell lung cancer in Japanese real-world settings., (© The Author(s) 2024. Published by Oxford University Press.)

Introduction: Immune checkpoint inhibitor (ICI)-based treatment has become standard treatment for patients with advanced NSCLC. We aimed to determine the survival benefit of upfront radiotherapy for brain metastases (BMs) in patients with NSCLC who received ICI alone (ICI-alone) or with chemotherapy (ICI-chemo)., Methods: This study included consecutive patients with NSCLC having BMs who received ICI alone or ICI-chemo at 50 institutes between February 2017 and September 2021. The presence of BMs was confirmed by imaging before treatment. Treatment outcomes were compared between patients who did and did not receive upfront radiotherapy for BMs. Potential confounding factors were adjusted between the groups through inverse probability treatment weighting (IPTW) analysis and overlap weighting (OW) analysis with propensity scores., Results: Patients were grouped as ICI-alone cohort, 224 patients (upfront-radiotherapy group, 135 patients; no-radiotherapy group, 89 patients) and ICI-chemo cohort, 367 patients (upfront-radiotherapy group, 212 patients; no-radiotherapy group, 155 patients). In the ICI-alone cohort, the overall survival of the upfront-radiotherapy group was significantly longer than that of the no-radiotherapy group (IPTW-adjusted hazards ratio [HR] = 0.45 [95% confidence interval [CI]: 0.29-0.72], OW-adjusted HR = 0.52 [95% CI: 0.35-0.77]). In contrast, in the ICI-chemo cohort, the OS of the upfront-radiotherapy group was not significantly different from that of the no-radiotherapy group (IPTW-adjusted HR = 1.02 [95% CI: 0.70-1.48], OW-adjusted HR = 0.93 [95% CI: 0.65-1.33])., Conclusions: Upfront radiotherapy for BMs was associated with longer overall survival in patients with NSCLC who received ICI alone; however, it did not exhibit survival benefits in the patients who received ICI-chemo., Competing Interests: Dr. Tozuka has received honoraria from Chugai Pharmaceutical and AstraZeneca. Dr. Minegishi has received honoraria from AstraZeneca, Boehringer Ingelheim Japan, Eli Lilly Japan, Taiho Pharmaceutical, Chugai Pharmaceutical, Ono Pharmaceutical, Eisai, Bristol-Myers Squibb, Daiichi-Sankyo, Nippon Kayaku, Takeda Pharmaceutical, and GlaxoSmithKline. Dr. Yamaguchi has received honoraria from Ono Pharmaceutical Co. Ltd., Bristol-Myers Squibb Co. Ltd., and Chugai Pharmaceutical Co. Ltd. Dr. Toi has received honoraria from Bristol-Myers Squibb Company, Ono Pharmaceutical Co., Ltd., Merck Sharp & Dohme K.K., AstraZeneca Plc., Chugai Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Pfizer Inc., and Kyowa Kirin Co., Ltd. Dr. Tamura has received honoraria from Merck Sharp & Dohme (Merck & Co., Inc.), Chugai Pharmaceutical Co., Ltd., AstraZeneca K.K., and Ono Pharmaceutical Co., Ltd. Dr. Sakai has received grants from Eli Lilly Japan K.K.; and has received honoraria from AstraZeneca K.K., Nippon Boehringer Ingelheim Co., Ltd., Chugai Pharmaceutical Co., Ltd., Pfizer Japan Inc., and ThermoFisher Scientific K.K. Dr. Watanabe has received funding from Bristol-Myers Squibb K.K. and 10.13039/501100013170Ono Pharmaceutical Co., Ltd.; has received grants from Boehringer Ingelheim and 10.13039/100018046Nippon Kayaku; and has received honoraria from Eli Lilly, Novartis Pharma, Chugai Pharma, Bristol-Myers, Ono Pharmaceutical, Daiichi-Sankyo, Taiho Pharmaceutical, Nippon Kayaku, Kyowa Kirin, Merck, Takeda Pharmaceutical, Celltrion, and AstraZeneca. Dr. Morita has received honoraria from AstraZeneca K.K, Bristol-Myers Squibb Company, Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Merck Sharp & Dohme K.K., Pfizer Japan Inc., and Taiho Pharmaceutical Co., Ltd. Dr. Kobayashi has received honoraria from AstraZeneca, Daiichi-Sankyo Pharmaceutical Co., and Takeda Pharmaceutical Co.; and is the Board Chairman in NPO North East Japan Study Group. Dr. Seike has received honoraria from AstraZeneca, Merck Sharp & Dohme K.K, Chugai Pharmaceutical, Taiho Pharmaceutical, Eli Lilly, Ono Pharmaceutical, Bristol-Myers Squibb, Nippon Boehringer Ingelheim, Pfizer, Novartis, Takeda Pharmaceutical, Kyowa Hakko Kirin, Nippon Kayaku, Daiichi-Sankyo Company, Merck Biopharma, and Amgen Inc.; and has received research funding from 10.13039/100009954Taiho Pharmaceutical, 10.13039/100010795Chugai Pharmaceutical, Eli Lilly, 10.13039/100017346Nippon Boehringer Ingelheim, Nippon Kayaku and 10.13039/501100004095Kyowa Hakko Kirin. The remaining authors declare no conflict of interest., (© 2024 by the International Association for the Study of Lung Cancer.)

Introduction: Fosnetupitant is a novel neurokinin 1 receptor antagonist (NK 1 RA) with favorable antiemetic efficacy in patients receiving emetogenic chemotherapy. This study assessed the efficacy of fosnetupitant in combination with palonosetron and dexamethasone and identified risk factors for chemotherapy-induced nausea and vomiting (CINV) for up to 168 h after treatment using pooled data from Japanese studies., Methods: A pooled analysis of randomized phase II and phase III studies was performed to compare the efficacy of fosnetupitant and fosaprepitant in patients receiving cisplatin-based chemotherapy. The complete response (CR; no vomiting and no rescue medication) rate, CINV risk factors in various phases (0-120, 0-168, and 120-168 h), and impact of the number of risk factors on the time to treatment failure (TTF) were examined in the overall and NK 1 RA evaluable populations., Results: In the combined cohort of NK 1 RA evaluable patients (n = 980), the CR rate at 0-168 h was significantly better in the fosnetupitant 235 mg group than in the fosaprepitant group (rate difference = 6.8%, 95% confidence interval = 1.0-12.7, p = 0.022). In the overall (n = 1368) and NK 1 RA evaluable populations, the CINV risk factor at 120-168 h was treatment failure in the first 120 h. TTF deteriorated as the number of identified CINV risk factors increased., Conclusion: This analysis revealed that fosnetupitant could have long-acting antiemetic potency (> 120 h) and indicated the importance of antiemetic therapy at 0-120 h for CINV up to 168 h after chemotherapy., (© 2023. The Author(s).)

Background: There is no well-established late-line treatment for advanced nonsquamous non-small cell lung cancer (NSCLC). Therefore, we retrospectively determined the efficacy and safety of platinum rechallenge with paclitaxel-carboplatin and bevacizumab in patients with nonsquamous NSCLC as a late-line therapy in a clinical setting., Methods: Thirty patients with nonsquamous NSCLC who received paclitaxel-carboplatin with bevacizumab therapy as a late-line treatment at Sendai Kousei Hospital (Miyagi, Japan) between December 2011 and December 2021 were enrolled into the study. The efficacy and safety of this treatment were evaluated. The patients were further categorized into responders and nonresponders, and predictive factors of treatment response were estimated., Results: The median progression-free survival (PFS) was 6.3 (range, 4.9-6.8) months, and the median overall survival (OS) was 11.8 (range, 7.2-17.2) months. There were no significant differences in PFS and OS between patients with and those without epidermal growth factor receptor mutations. In the univariate analyses of this study, responders were younger than nonresponders (p = 0.012). No fatal adverse events were reported., Conclusions: With the increase in the number of treatment options in recent years, the sequence of treatments and overall therapeutic strategy are becoming increasingly important. Thus, platinum rechallenge with paclitaxel-carboplatin and bevacizumab, a late-line treatment for patients with nonsquamous NSCLC, may be an effective therapeutic option., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background:  First-line treatment of nonsquamous non-small cell lung cancer (NSCLC) has undergone a paradigm shift to platinum combination therapy together with immune checkpoint inhibitors (ICIs). However, phase III studies of combinations of cytotoxic chemotherapy and ICIs have included only patients with maintained organ function, not those with renal impairment., Methods: Cytotoxic chemotherapy-naïve advanced nonsquamous NSCLC patients aged 20 years or older with impaired renal function (creatinine clearance of 15 to 45 mL/min) are prospectively registered in this single-arm phase II study and receive combination therapy with carboplatin, nanoparticle albumin-bound (nab-) paclitaxel, and atezolizumab. Individuals with known genetic driver alterations including those affecting EGFR, ALK, ROS1, BRAF, MET, RET, and NTRK are excluded. We plan to enroll 40 patients over 2 years at 32 oncology facilities in Japan. The primary end point is confirmed objective response rate., Discussion: If the study demonstrates efficacy and safety of carboplatin/nab-paclitaxel/atezolizumab, then this combination regimen may become a treatment option even for nonsquamous NSCLC patients with impaired renal function., Trial Registration: Registered with Japan Registry for Clinical Trials on 25 February 2021 (jRCTs071200102)., (© 2022. The Author(s).)

Purpose: To explore the efficacy of retreatment with immune checkpoint inhibitors (ICI) in patients with advanced non-small cell lung cancer (NSCLC) who responded to prior ICI and had adequate ICI-free interval., Patients and Methods: Patients with advanced NSCLC who had achieved complete response (CR), partial response (PR), or stable disease for ≥6 months with prior ICI therapy preceding progression were prospectively enrolled. All patients should have had ICI-free interval ≥60 days before registration. Patients were treated with nivolumab (240 mg) every 2 weeks until progression. The primary endpoint was overall response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival, and safety (Trial Identifier, UMIN000028561)., Results: Sixty-one patients were enrolled during October 2017 to February 2020, with 59 analyzed for efficacy. Regarding prior ICI, 41 patients had CR or PR. Median treatment on ICI and median ICI-free intervals were 8.1 months and 9.2 months, respectively. Twenty patients experienced immune-related adverse events (irAE) that required discontinuation of prior ICI. Nivolumab retreatment demonstrated ORR of 8.5% [95% confidence interval (CI), 2.8-18.7%] and median PFS of 2.6 months (95% CI, 1.6-2.8 months) while 5 responders had 11.1 months of median PFS. In the multivariate analysis, ICI-free interval was the only predictive factor of PFS (HR, 2.02; P = 0.02), while prior efficacy or history of irAE was not. Common adverse events were skin disorders (23%), malaise (20%), and hypoalbuminemia (15%)., Conclusions: Even in patients who initially responded to prior ICI and had ICI-free interval, once resistance occurred, retreatment with nivolumab had limited efficacy., (©2022 The Authors; Published by the American Association for Cancer Research.)