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Background: Chemotherapy-induced anorexia is a common occurrence in patients undergoing treatment for advanced lung cancer. However, the relationship between chemotherapy-induced anorexia and weight loss during platinum-based chemotherapy combined with immune checkpoint inhibitors is unclear. This study explored the relationship between chemotherapy-induced anorexia and therapeutic outcomes in patients with stage IV non-small-cell lung cancer undergoing platinum-based chemotherapy combined with immune checkpoint inhibitors., Methods: The study retrospectively reviewed the medical records of 106 patients with stage IV non-small-cell lung cancer treated with platinum-based chemotherapy and immune checkpoint inhibitors between January 2019 and October 2022. The incidence of weight loss and its association with treatment efficacy was assessed in the chemotherapy-induced anorexia group. Chemotherapy-induced anorexia, nausea, and vomiting were evaluated using Common Terminology Criteria for Adverse Events v 5.0. Progression-free and overall survival were used to measure treatment efficacy., Results: Chemotherapy-induced anorexia was observed in 13.2% of patients. These patients exhibited significant weight loss at 6 and 9 weeks after treatment initiation compared to those in the non-chemotherapy-induced anorexia group. Progression-free and overall survival were shorter in the chemotherapy-induced anorexia group than in the non-chemotherapy-induced anorexia group, but the difference was not statistically significant., Conclusions: Chemotherapy-induced anorexia was associated with significant weight loss and reduced treatment efficacy in patients with stage IV non-small-cell lung cancer. These results highlight the importance of implementing robust supportive care for chemotherapy-induced anorexia to mitigate weight loss and uphold treatment effectiveness during platinum-based chemotherapy combined with immune checkpoint inhibitors., (© 2024 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

Background: The AmoyDx Pan lung cancer PCR panel (AmoyDx PLC panel) has been approved as a companion diagnostic tool for multiple anticancer agents in patients with non-small cell lung cancer (NSCLC). However, the suitability of cytology specimens as samples for the AmoyDx PLC panel remains unclear. We evaluated the performance of frozen cell pellets from cytology specimens (FCPs) in the Amoy 9-in-1 assay, a preapproval assay of the AmoyDx PLC panel., Methods: We retrospectively collected data of NSCLC patients enrolled in LC-SCRUM-Asia from the Shizuoka Cancer Center between September 2019 and May 2021., Results: A total of 49 cases submitted FCPs for evaluation of oncogenic driver alterations and were assessed using Amoy 9-in-1 and next-generation sequencing (NGS) assays. The success rates of DNA and RNA analyses using the Amoy 9-in-1 were both 100%, compared with 86% and 45%, respectively, using NGS assays. Oncogenic driver alterations were detected in 27 (55%) and 23 (47%) patients using Amoy 9-in-1 and NGS, respectively. No inconsistent results were observed among 19 cases in which both assays showed successful detection. In the remaining 30 cases, 10 had inconsistent results: nine oncogenic driver alterations (3 MET, 2 ALK, 2 ROS1, and 2 KRAS) were detectable only in Amoy 9-in-1, and one epidermal growth factor receptor (EGFR) mutation was detectable only in NGS., Conclusion: FCPs can be successfully used in the AmoyDx PLC panel, with higher success rate compared with the NGS assay. The AmoyDx PLC panel may be an option in cases when insufficient tissue sample is available for the NGS assay., (© 2024 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

Background: Which patients benefit from the addition of immune checkpoint inhibitors (ICIs) to chemotherapy for small cell lung cancer (SCLC) remains unclear. There have been few reports on the efficacy of ICIs based on conventional immunohistochemical neuroendocrine (NE) markers (synaptophysin, chromogranin A, and neural cell adhesion molecule [NCAM]). In the present study, we aimed to analyze the relationship between the expression of immunohistochemical NE markers and the efficacy of ICIs in patients with extensive disease (ED)-SCLC, to assess whether conventional NE markers are predictive of ICIs., Methods: Patients with untreated ED-SCLC who received first-line therapy at the Shizuoka Cancer Center between November 2002 and July 2021 were retrospectively reviewed. We evaluated the efficacy of first-line chemotherapy according to the expression status of each immunohistochemical NE marker in patients treated with ICI plus chemotherapy (ICI-chemo group) and with chemotherapy alone (chemo group)., Results: A total of 227 patients were included in the ICI-chemo and chemo groups, respectively. The progression-free survival (PFS) tended to be better in patients in the ICI-chemo group than those treated with chemotherapy alone in patients with NE marker-positive SCLC. In particular, it was statistically significant in patients with chromogranin A-positive SCLC (p = 0.036). In patients with NE marker-negative SCLC, no significant differences were observed in PFS between the two groups. There were no significant differences in overall survival (OS), regardless of the expression of any conventional NE marker., Conclusion: Our study suggests that the efficacy of ICIs in addition to chemotherapy may be poor in patients with NE marker-negative SCLC., (© 2024 The Authors. Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

Background: Amrubicin (AMR) regimens have shown efficacy as second-line treatment in patients with small cell lung cancer (SCLC); however, adverse events such as febrile neutropenia (FN) sometimes preclude their use. Further, the safety and efficacy of AMR with primary prophylactic pegfilgrastim (P-PEG) have not been sufficiently evaluated. In this study, we evaluated the safety and efficacy of AMR with or without P-PEG as second-line chemotherapy for SCLC., Methods: We retrospectively reviewed patients with SCLC who received AMR as second-line chemotherapy at Shizuoka Cancer Center, between December 2014 and November 2021. Based on presence/absence of P-PEG in their regimen, patients (n = 60) were divided into P-PEG (n = 21) and non-P-PEG groups, and their clinical outcomes were evaluated., Results: Median of AMR treatment cycles was five (range: 1-39 cycles) in P-PEG group and four (range: 1-15 cycles) in non-P-PEG group. The incidence of FN (4.8% vs. 30.8%; p = 0.02) and AMR dose reduction because of adverse events (4.8% vs. 25.6%; p = 0.08) were lower in the P-PEG group than in the non-P-PEG group. The objective response rates were 52.4% and 30.8%, and median progression-free and overall survival were 4.7 and 3.0 months, and 9.6 and 6.8 months, in the P-PEG and non-P-PEG groups, respectively., Conclusions: AMR with P-PEG as second-line chemotherapy for SCLC reduced the incidence of FN at a maintained AMR dose intensity and was associated with favorable tumor responses and survival outcomes. P-PEG should be considered for patients treated with AMR for SCLC including refractory relapsed SCLC., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Carboplatin plus etoposide is a standard treatment for older extensive-stage small-cell lung cancer (ES-SCLC) patients with performance status (PS) 2. However, older patients often exhibit poor PS (3, 4), and the treatment effect in them is poorly understood. To determine the therapeutic efficacy and safety of carboplatin plus etoposide therapy for this population, we retrospectively analyzed 63 patients with ES-SCLC with PS ≥2, aged ≥71 years, who had received first-line carboplatin plus etoposide therapy. We compared the treatment efficacy and safety in patients with baseline PS 2 versus those with PS 3-4. In the PS 2 (38 patients) and PS ≥3 (25 patients) groups, the overall response rate was 71.1% and 72.0%, median progression-free survival was 4.6 and 3.1 months, and overall survival was 7.7 and 5.1 months, respectively. PS improved to 0-1 post-treatment in 65.8% and 48.0% of the patients in the PS 2 and PS ≥3 groups, respectively. Patients with PS ≥3 showing improved PS had a progression-free survival of 6.1 months. A higher incidence of grade ≥3 decreased neutrophil counts, febrile neutropenia, and treatment-related death was observed in the PS ≥3 group. The progression-free survival of patients administered prophylactic granulocyte colony-stimulating factor (G-CSF) was 5.2 and 6.1 months in the PS2 and PS ≥3 groups. Overall, carboplatin plus etoposide therapy provided comparable tumor shrinkage, but shorter progression-free and overall survival in older ES-SCLC patients with PS ≥3 than in those with PS 2. Thus, supportive care, such as prophylactic G-CSF administration, may be necessary to ensure safety and survival., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: Cancer cachexia and tumor burden predict efficacies of programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors and chemotherapy or pembrolizumab in non-small cell lung cancer (NSCLC). There are no predictive models that simultaneously assess cancer cachexia and tumor burden., Methods: In the present retrospective study, we reviewed the medical records of patients with advanced NSCLC who received cancer immunotherapy as first-line systemic therapy. Clinical immune predictive scores were defined according to multivariate analysis of progression-free survival (PFS) and overall survival (OS)., Results: A total of 157 patients were included in the present study (75 treated with PD-1/PD-L1 inhibitors + chemotherapy; 82, pembrolizumab monotherapy). Multivariate analysis for PFS revealed that PD-L1 tumor proportion scores <50%, a total target lesion diameter ≥76 mm, and cancer cachexia were independently associated with poor PFS. Multivariate analysis for OS revealed that ≥4 metastases and cancer cachexia were significantly associated with poor OS. In the immune predictive model, the median PFS was 21.7 months in the low-risk group (N = 41); 7.6 in the medium-risk group (N = 64); and 3.0 in the high-risk group (N = 47). The median OS were not reached, 22.4 and 9.1 months respectively. Our immune predictive model was significantly associated with PFS (p < 0.001) and OS (p < 0.001)., Conclusion: We proposed the immune predictive model, including tumor burden and cancer cachexia, which may predict the efficacy and survival outcome of first-line immunotherapy in advanced NSCLC., (© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: Adipose tissue induces inflammation, which desensitizes the efficacy of immunotherapy. However, several reports show that the therapeutic effect of programed cell death 1 (PD-1)/programed death-ligand 1 (PD-L1) inhibitor(s) monotherapy is significantly better in obese patients. Therefore, the effect of adipose tissue on immunotherapy is unclear., Methods: In this study, we retrospectively reviewed patients with advanced non-small cell lung cancer (NSCLC) who received PD-1/PD-L1 inhibitor monotherapy between May 2016 and December 2018. We classified patients into total adipose tissue maintenance or loss groups according to adipose tissue change during the 6 months before treatment and compared the therapeutic effect of PD-1/PD-L1 inhibitors between these groups along with the presence or absence of cachexia, a poor prognostic factor., Results: Of the 74 patients, 40 (54.1%) were cachexic. Among cachexic patients, we found no clear difference in the overall response rate (ORR) and progression-free survival (PFS) between the total adipose tissue maintenance and loss group. However, among noncachexic patients, the total adipose tissue loss group had a higher ORR (64.7% vs. 23.5%, p < 0.05) and longer PFS (18.5 months vs. 2.86 months, p = 0.037) than the maintenance group., Conclusions: This study showed that decreasing adipose tissue without cachexia might favor the therapeutic effects of immunotherapy., (© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: Atezolizumab is a programmed death-ligand 1 (PD-L1) targeted monoclonal antibody that inhibits PD-L1 interacting with its receptors PD-1 and B7-1, thereby enhancing anticancer immunity. Some real-world efficacy and safety studies of anti-PD-1 antibody have been previously reported. However, there have been no reports investigating the efficacy of atezolizumab monotherapy in clinical practice which have focused on performance status and previous anti-PD-1 antibody treatment., Methods: We retrospectively reviewed consecutive advanced NSCLC patients who received atezolizumab monotherapy between April 2018 and February 2019 at eight institutions. A total of 152 patients with NSCLC were enrolled in this study., Results: A total of 38 patients (25%) had already been treated with anti-PD-1 treatment (nivolumab or pembrolizumab) before atezolizumab. The median OS and TTF was 384 days (12.8 months) (95% confidence interval [CI]: 206-424), and 42 days (1.4 months) (95% CI: 27-56) in all patients, respectively. ECOG PS 0 had significantly longer OS (median OS; not reached, p < 0.0001) and TTF (median TTF; 63 days, p = 0.012) compared with PS 1 or 2-3. Most retreated patients were unable to continue atezolizumab for a longer period, but seven patients (18.4%) were able to continue atezolizumab over four months as an ICI retreatment., Conclusions: In previously treated advanced NSCLC patients, atezolizumab monotherapy demonstrated good efficacy and safety regardless of heavily treated patients in real-world clinical practice, and ECOG PS 0 was a favorable predictive factor. The efficacy of retreatment with atezolizumab was limited but was well tolerated in patients treated with prior anti-PD-1 antibody., (© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)