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Background S‐1 and pemetrexed (PEM) are key treatments for non‐small cell lung cancer (NSCLC). However, the mechanism of anticancer activity of S‐1 and PEM is similar. Cross‐resistance between S‐1 and PEM is of concern. This exploratory study was designed to evaluate the treatment effect of S‐1 following PEM‐containing treatment. Methods This retrospective study included patients with advanced (c‐stage III or IV, UICC seventh edition) or recurrent NSCLC who received S‐1 monotherapy following the failure of previous PEM‐containing chemotherapy at six hospitals in Japan. The primary endpoint of the study was the overall response rate (ORR). The secondary endpoint was the disease control rate (DCR), time to treatment failure (TTF), progression‐free survival (PFS), and overall survival (OS). Results A total of 53 NSCLC patients met the criteria for inclusion in the study. Forty‐six patients had adenocarcinoma (88.7%) and no patients had squamous cell carcinoma. Thirty‐one patients (58.5%) received the standard S‐1 regimen and 18 patients (34.0%) received the modified S‐1 regimen. ORR was 1.9% (95% confidence interval [CI]: 0.00%–10.1%). Median TTF, PFS, and OS were 65, 84, and 385 days, respectively. Conclusions Although there were several limitations in this study, the ORR of S‐1 after PEM in patients with nonsquamous (non‐SQ) NSCLC was low compared to the historical control. One of the options in the future might be to avoid S‐1 treatment in PEM‐treated patients who need tumor shrinkage., Predictive factor of S‐1 and PEM is TS expression.Cross‐resistance between S‐1 and PEM is of concern.This study was designed to evaluate the treatment effect of S‐1 following PEM‐containing treatment.ORR of S‐1 after PEM was low.

Introduction: Immunotherapy with immune checkpoint inhibitors (ICI) is the standard of care for advanced non-small-cell lung cancer (NSCLC) without driver gene alterations. However, survival benefits with ICI are limited to a small subset of NSCLC patients, and particularly ICI combinations with cytotoxic agents produce serious physical and large financial toxicities. Tumor PD-L1 expression levels/proportion score (TPS) are universally used as predictive biomarkers in ICI monotherapy response and outcomes. However, PD-L1/TPS assays are imperfect because of low analytical validity and reproducibility due to the visual-scoring system by pathologists. Therefore, additional biomarkers are urgently needed to predict ICI therapy response and outcomes. Recently, we reported that serum antibodies (Abs) against NY-ESO-1 and XAGE1 cancer-testis antigens were probably useful biomarkers in the prediction of clinical benefits with anti-PD-1 monotherapy for NSCLC (J Thorac Oncol, 2019). Additionally, we developed a fully automated immunoassay system (HISCLTM) to measure the Abs easily and rapidly (Sakai Y, et al. Clin Chim Acta 2021). In this study, we retrospectively examined whether the Abs measured by HISCLTM predict the clinical benefits with ICI monotherapy for NSCLC.Patients and Methods: Sera were obtained from controls of non-malignant lung diseases (n=75) and healthy subjects (n=100), and advanced NSCLC patients (n=263) to to determine a cutoff value in HISCLTM. In NSCLC patients analyzed here (n=78), sera were obtained before anti-PD-1 monotherapy with nivolumab in second-line or later settings. The serum NY-ESO-1/XAGE1 Abs were measured by HISCLTM, and we examined the relationships between the Abs levels, objective response rate (ORR), progression free survival (PFS), and overall survival (OS) after nivolumab monotherapy.Results: NY-ESO-1/XAGE1 Abs levels in NSCLC patients (n=263) were significantly higher than those in the controls (n=175). A cutoff value was determined as the Abs level of 10 SU/mL, calculated from the Abs values in the controls. The Abs (≥ 10 SU/mL) were detected in 21/78 (27%) of the NSCLC patients treated with nivolumab, and one patient had both NY-ESO-1 and XAGE1 Ab. An ORR was 62%, 16%, and 29% in the Abs-positives, the Abs-negatives, and overall, respectively. The Abs levels in responders were significantly higher than those in non-responders. The NSCLC patients with high-Abs values (≥ 10 SU/mL) had significantly better survivals with nivolumab monotherapy than those with low-Abs (PFS, HR 0.51, 95%CI 0.31-0.83, p < 0.01; OS, HR 0.51, 95%CI 0.31-0.84, p < 0.01). Interestingly, a few NSCLC patients with both high-Abs and driver genes responded well to nivolumab.Conclusions: Serum NY-ESO-1/XAGE1 Abs measured by HISCLTM are potential biomarkers that predict clinical benefits with anti-PD-1 monotherapy for NSCLC, even including driver genes. These findings warrant further biomarker studies using NY-ESO-1/XAGE1 Abs in clinical trial and practice of NSCLC immunotherapy. Citation Format: Kanako Sakaeda, Koji Kurose, Minoru Fukuda, Nanae Sugasaki, Akitoshi Kinoshita, Takashi Kitazaki, Masaaki Fukuda, Takeshi Masuda, Noboru Hattori, Yusuke Atarashi, Yumiko Sakai, Yasuhiro Irino, Mami Yamaki, Toshiyuki Sato, Hiroshi Mukae, Toru Oga, Mikio Oka. Development of automated immunoassay to detect serum biomarkers predicting response to immune checkpoint inhibitors in NSCLC [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy; 2022 Oct 21-24; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(12 Suppl):Abstract nr A61.

BACKGROUND The first-line treatment for squamous cell lung cancer (SCC) has not necessarily been established; however, our previous exploratory study suggested that the combination of nedaplatin and amrubicin would be a promising treatment approach for patients with SCC. Therefore, a phase II study of this chemotherapeutic combination was designed to evaluate its efficacy and safety for treatment-naive patients with advanced SCC. METHODS A total of 21 treatment-naive patients with stage IIIB/IV or postoperative recurrent SCC were enrolled from six institutions. Nedaplatin (100 mg/m2 ) on day 1 and amrubicin (25 mg/m2 ) on days 1-3 were administered intravenously every 4 weeks. The primary endpoint was overall response rate (ORR), while the secondary endpoints included overall survival (OS), progression-free survival (PFS), and drug toxicities. RESULTS Partial response was observed in seven of 21 cases (ORR, 33.3%; 95% confidence interval [CI], 14.5-52.2). Disease control rate, which includes stable disease, was 71.4%. Median OS and PFS was 14.6 and 4.1 months, respectively. This regimen did not cause any treatment-related deaths. Grade 3/4 neutropenia developed in 8 of 21 cases (38.1%); however, febrile neutropenia developed in only 9.5% of the cases. Grade 3/4 gastrointestinal or neuromuscular toxicities were not observed. CONCLUSION The efficacy of the combination of nedaplatin and amrubicin was comparable to that of other conventional chemotherapeutic regimens for treatment-naive patients with advanced SCC, and no severe gastrointestinal or neuromuscular toxicities were observed. This combination therapy may be an alternative treatment approach, particularly in patients who cannot tolerate gastrointestinal or neuromuscular toxicities.

BACKGROUND Focal nodular hyperplasia (FNH) of the liver is a rare benign nodular lesion that arises in women of reproductive age. Although a role of female hormones has been suggested, their influence on the course of FNH has remained controversial. CASE REPORT A 44-year-old woman with a 12-year history of oral contraceptive use was referred to our hospital for examination of an asymptomatic liver mass (3 cm in diameter) identified by computed tomography. We diagnosed FNH using imaging methods and fine-needle biopsy. Oral contraceptives were discontinued because the mass increased over a period of 21 months. Four months later, the mass had decreased in size, indicating that FNH can spontaneously regress when oral contraceptives are discontinued. CONCLUSIONS Discontinuation of oral contraceptives use can reduce the size of FNH, as in this case., The American journal of case reports, 20, pp.1124-1127; 2019

e20023 Background: Amrubicin and cisplatin is one of active regimens for patients with extensive-disease small cell lung cancer (ED-SCLC). Combined modality of combination chemotherapy and concurrent thoracic radiotherapy has been recognized as standard treatment for LD-SCLC. This study aimed to determine the maximum tolerated dose (MTD), and dose limiting toxicity (DLT) of amrubicin and cisplatin with concurrent TRT in LD-SCLC. Methods: Patients fulfilling the following eligibility criteria were enrolled: chemotherapy-naïve, PS0-1, age = < 75, LD-SCLC, and adequate organ function. Patients received escalating doses of amrubicin on days 1, 2, and 3, under a fixed 60 mg/m2 of cisplatin on day 1. Four cycles of chemotherapy were repeated every 4 weeks. TRT of once-daily 2Gy/day commenced on day 2 of the first cycle of chemotherapy. The initial doses of amrubicin was 20 mg/m2, and the dose was escalated to 25 and 30 mg/m2. Results: Eight patients (male/female = 3/5; PS 0/1 = 4/4; median age (range) = 68.5 (60-73)) were enrolled at three dose levels. Three patients in 20 mg/m2 and three patients in 25 mg/m2 dose levels did not experienced DLT. Two of two patients in 30 mg/m2 dose level experienced DLTs. The presentation of DLTs included grade4 neutropenia and leukopenia lasting more than four days. Evaluation of responses were 7 partial response and 1 progressive disease (response rate 87.5%) and the median survival time was 24.7 months. The MTD of amrubicin and cisplatin were determined as 30 mg/m2 and 60 mg/m2. A dose of 25 mg/m2 amrubicin and cisplatin 60 mg/m2 was recommended in this regimen. Conclusions: This regimen with concurrent TRT in LD-SCLC is associated with an acceptable tolerability profile, and warrants evaluation in the phase II setting. Clinical trial information: UMIN000005816.