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Purpose: The addition of cytotoxic chemotherapy to immune-checkpoint inhibitor (ICI) may enhance antitumor effects. We conducted an open-label randomized phase II/III study to evaluate nivolumab + docetaxel combination therapy in comparison with nivolumab monotherapy for previously treated ICI-naïve non–small cell lung cancer (NSCLC). Patients and Methods: The primary endpoint of the phase III study was overall survival (OS), and the secondary endpoints included progression-free survival (PFS), overall response rate (ORR), and toxicity. As ICI and platinum-doublet combination chemotherapy was approved in the first-line setting during this study, patient accrual was discontinued. Results: One hundred twenty-eight patients (each arm, n = 64) were included in the full analysis set. The median OS in nivolumab (arm A) and nivolumab + docetaxel (arm B) was 14.7 months (95% CI, 11.4–18.7) and 23.1 months (95% CI, 16.7–NR), respectively. The HR for OS was 0.63 (90% CI, 0.42–0.95; P = 0.0310). The median PFS in arms A and arm B was 3.1 months (95% CI, 2.0–3.9) and 6.7 months (95% CI, 3.8–9.4), respectively. The HR for progression was 0.58 (95% CI, 0.39–0.88; P = 0.0095). The ORR was 14.0% (95% CI, 6.3–25.8) in arm A and 41.8% (95% CI, 28.7–55.9) in arm B. Hematotoxicity and gastrointestinal adverse events were more common in arm B than in arm A. Two treatment-related deaths were observed, including one patient in arm A who died of pneumonitis and one in arm B who died of myocarditis. Conclusions: Despite a slightly elevated toxicity, the addition of docetaxel to nivolumab has significantly prolonged the OS and PFS of patients with previously treated ICI-naïve NSCLC.

Supplementary Data from A Randomized Comparison of Nivolumab versus Nivolumab + Docetaxel for Previously Treated Advanced or Recurrent ICI-Naïve Non–Small Cell Lung Cancer: TORG1630

Purpose:The addition of cytotoxic chemotherapy to immune-checkpoint inhibitor (ICI) may enhance antitumor effects. We conducted an open-label randomized phase II/III study to evaluate nivolumab + docetaxel combination therapy in comparison with nivolumab monotherapy for previously treated ICI-naïve non–small cell lung cancer (NSCLC).Patients and Methods:The primary endpoint of the phase III study was overall survival (OS), and the secondary endpoints included progression-free survival (PFS), overall response rate (ORR), and toxicity. As ICI and platinum-doublet combination chemotherapy was approved in the first-line setting during this study, patient accrual was discontinued.Results:One hundred twenty-eight patients (each arm, n = 64) were included in the full analysis set. The median OS in nivolumab (arm A) and nivolumab + docetaxel (arm B) was 14.7 months (95% CI, 11.4–18.7) and 23.1 months (95% CI, 16.7–NR), respectively. The HR for OS was 0.63 (90% CI, 0.42–0.95; P = 0.0310). The median PFS in arms A and arm B was 3.1 months (95% CI, 2.0–3.9) and 6.7 months (95% CI, 3.8–9.4), respectively. The HR for progression was 0.58 (95% CI, 0.39–0.88; P = 0.0095). The ORR was 14.0% (95% CI, 6.3–25.8) in arm A and 41.8% (95% CI, 28.7–55.9) in arm B. Hematotoxicity and gastrointestinal adverse events were more common in arm B than in arm A. Two treatment-related deaths were observed, including one patient in arm A who died of pneumonitis and one in arm B who died of myocarditis.Conclusions:Despite a slightly elevated toxicity, the addition of docetaxel to nivolumab has significantly prolonged the OS and PFS of patients with previously treated ICI-naïve NSCLC.

Supplementary Figure from A Randomized Comparison of Nivolumab versus Nivolumab + Docetaxel for Previously Treated Advanced or Recurrent ICI-Naïve Non–Small Cell Lung Cancer: TORG1630

Dacomitinib is the second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) for mutant non-small cell lung cancer (NSCLC). EGFR-TKIs are often re-administered in Japan after the disease progression prior EGFR-TKI. There is little evidence of dacomitinib in rechallenge setting. This study evaluated clinical outcomes of dacomitinib in rechallenge setting.Patients who received dacomitinib for advanced EGFR-mutant NSCLC who had progressed after EGFR-TKI in nine institutions in Japan were included in the analyses.In total, 43 patients were analyzed. The median progression-free survival (PFS) was 4.3 months (95% confidence interval [CI], 2.5-5.6). The overall survival (OS) was 10.5 months (95% CI, 7.4-not reached). The overall response rate was 25.5% (95% CI, 13.1-33.7). Subset analysis indicated that patients with EGFR exon 21 L858R showed longer PFS than those with EGFR exon 19 deletion (5.8 vs. 4.1 months) (p = 0.018). The most common adverse events leading to dose modification were diarrhea, paronychia, rash, and oral mucositis.In the real practice in Japan, dacomitinib showed a worthwhile treatment option for NSCLC patients with EGFR mutation after failure of previous EGFR-TKI. The benefit was especially pronounced in patients with the exon 21 mutation.

Summary Background Bevacizumab is a promising candidate for combination treatment with epidermal growth factor receptor tyrosine-kinase inhibitors (eg, erlotinib), which could improve outcomes for patients with metastatic EGFR-mutant non-small-cell lung cancer (NSCLC). We have previously shown in NEJ026, a phase 3 trial, that the combination of bevacizumab plus erlotinib significantly prolonged progression-free survival compared with erlotinib alone in these patients. In further analyses, we aimed to examine the effects of bevacizumab–erlotinib on overall survival, time from enrolment to progressive disease during second-line treatment or death, and quality of life. Methods This open-label, randomised, multicentre, phase 3 trial (NEJ026) was done in 69 hospitals and medical, community-based centres across Japan. Eligible patients had stage IIIB, stage IV, or postoperative recurrent, EGFR-mutant (exon 19 deletion or exon 21 Leu858Arg point mutation) NSCLC, had not previously received systemic chemotherapy, and were randomly assigned (1:1) by a computer-generated randomisation sequence and minimisation to receive either 150 mg oral erlotinib once daily plus 15 mg/kg intravenous bevacizumab once every 21 days, or 150 mg oral erlotinib once daily, until disease progression or intolerable toxicity. Randomisation was stratified according to sex, smoking status, EGFR mutation subtype, and clinical disease stage. All participants, investigators, and study personnel (including those assessing outcomes) were unmasked to treatment allocation. We report the secondary outcomes of overall survival and quality of life (the period from enrolment to confirmation of a minimally important difference on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-C30), and the exploratory outcome of time from enrolment to progressive disease during second-line treatment or death. Overall survival and the exploratory outcome were analysed in the modified intention-to-treat population, which comprised all randomly assigned patients who received at least one dose of the study drug and had response evaluations. Quality of life was analysed in patients in the modified intention-to-treat population who had completed the quality of life questionnaires. The trial is registered with the University Hospital Medical Information Network Clinical Trials Registry, UMIN000017069, and the Japan Registry of Clinical Trials, jRCTs031180056, and is currently closed. Findings Between June 3, 2015, and Aug 31, 2016, 228 patients were enrolled. 112 patients who received bevacizumab–erlotinib and 112 who received erlotinib only were included in the modified intention-to-treat population. At data cutoff (Nov 30, 2019) and a median follow-up of 39·2 months (IQR 23·9–43·5), the median overall survival was 50·7 months (95% CI 37·3–not estimable [NE]) in the bevacizumab–erlotinib group and 46·2 months (38·2–NE) in the erlotinib-only group (hazard ratio [HR] 1·007, 95% CI 0·681–1·490; p=0·97). In analysis of the exploratory outcome, after a median follow-up of 23·9 months (IQR 14·2–39·1), the median time from enrolment to progressive disease during second-line treatment or death was 28·6 months (95% CI 22·1–35·9) in the bevacizumab–erlotinib group and 24·3 months (20·4–29·1) in the erlotinib-only group (HR 0·773, 95% CI 0·562–1·065). The median time between enrolment and confirmation of a minimally important difference on the EORTC QLQ-C30 was 6·0 months (95% CI 5·2–11·3) in the bevacizumab–erlotinib group and 8·3 months (5·7–13·9) in the erlotinib-only group (p=0·47). Interpretation The addition of bevacizumab to erlotinib did not prolong survival in patients with metastatic EGFR-mutant NSCLC, but both treatment groups had relatively long survival durations. Why the addition of bevacizumab to erlotinib did not affect overall survival is unclear, but it is possible that the beneficial effects of combination therapy were not seen because overall survival was influenced by treatment regimens used after disease progression. Funding Chugai Pharmaceutical.

The therapeutic efficacy of cytotoxic anticancer drugs has been reported to be enhanced after immune checkpoint inhibitors (ICI) in non-small cell lung cancer; however, it is unclear whether the same is applicable for small cell lung cancer (SCLC). We evaluated the efficacy of second-line amrubicin (AMR) following first-line platinum-based chemotherapy and ICI combination therapy (chemo-ICI) in SCLC.We retrospectively enrolled consecutive patients with SCLC treated with AMR as a second-line following chemo-ICI as first-line between July 2019 and April 2021 from 16 institutions throughout Japan. We investigated the therapeutic effectiveness, safety, and efficacy-enhancing variables of AMR.Overall, 89 patients treated with AMR after first-line chemo-ICI were analyzed. The overall response rate (ORR) was 29.2% (95% confidence intervals [CI], 20.1-39.8) and median PFS (m PFS) was 2.99 months (95% CI, 2.27-3.65). Patients who relapsed more than 90 days after receiving first-line platinum combination therapy (sensitive relapse) exhibited greater ORR (58.3% vs. 24.7%, p = 0.035) and m PFS (5.03 vs. 2.56 months, p = 0.019) than patients who relapsed in90 days (refractory relapse). Grade 3 or higher adverse events were mainly hematological toxicity.Our study suggested that the therapeutic effect of AMR was not enhanced after ICI on SCLC. However, AMR may be effective in cases of sensitive relapse after chemo-ICI. There was no increase in severe toxicity associated with AMR after ICI.

Recently, the addition of antiprogrammed cell death-ligand 1 (PD-L1) monoclonal antibodies, including durvalumab and atezolizumab to platinum-based chemotherapy, has demonstrated clinical benefits in patients with untreated advanced small cell lung cancer (SCLC). However, these clinical trials comprised small populations of elderly patients with SCLC. Therefore, the safety of anti-PD-L1 immunotherapy plus platinum and etoposide in elderly patients remains unclear.This prospective, multicenter, single-arm study was designed to evaluate the safety and efficacy of durvalumab plus carboplatin and etoposide in untreated elderly patients (aged 75) with extensive stage (ES) SCLC. A total of 40 patients were recruited. Patients received up to four cycles of durvalumab 1500 mg and carboplatin at a dose equivalent to an area under the curve of 5 on day 1, and etoposide 80 mg/mThe present study was designed to evaluate the safety of durvalumab plus carboplatin and etoposide in elderly patients with ES-SCLC.

Background The association between the development of checkpoint inhibitor pneumonitis (CIP) with tumor response and survival has remained unclear so far. The aim of the present study was to evaluate the association between CIP and the clinical efficacy of anti‐programmed cell death‐1 antibody in patients with advanced non‐small cell lung cancer (NSCLC). Methods Between January 2016 and August 2019, 203 advanced NSCLC patients were administered with nivolumab or pembrolizumab. Comparisons were made between patients with and without CIP. We evaluated the time‐to‐treatment failure (TTF), progression‐free survival (PFS), and overall survival (OS). Results CIP was observed in 28 (14%) patients. CIP was associated with a longer PFS (18.9 months [95% confidence interval, CI: 8.7 months–not reached] vs. 3.9 months [95% CI: 3.4–5.1 months, p, This study aimed to evaluate the association between checkpoint inhibitor pneumonitis (CIP) and the clinical efficacy of anti‐programmed cell death‐1 monotherapy in patients with advanced non‐small cell lung cancer (NSCLC). CIP was associated with a longer PFS (18.9 months vs. 3.9 months, p

Introduction. Resistance against macrolide antibiotics in Mycoplasma pneumoniae is becoming non-negligible in terms of both appropriate therapy and diagnostic stewardship. Molecular methods have attractive features for the identification of Mycoplasma pneumoniae as well as its resistance-associated mutations of 23S ribosomal RNA (rRNA). Hypothesis/Gap Statement. The automated molecular diagnostic sytem can identify macrolide-resistant M. pneumoniae . Aim. To assess the performance of an automated molecular diagnostic system, GENECUBE Mycoplasma, in the detection of macrolide resistance-associated mutations. Methodology. To evaluate whether the system can distinguish mutant from wild-type 23S rRNA, synthetic oligonucleotides mimicking known mutations (high-level macrolide resistance, mutation in positions 2063 and 2064; low-level macrolide resistance, mutation in position 2067) were assayed. To evaluate clinical oropharyngeal samples, purified nucleic acids were obtained from M. pneumoniae -positive samples by using the GENECUBE system from nine hospitals. After confirmation by re-evaluation of M. pneumoniae positivity, Sanger-based sequencing of 23S rRNA and mutant typing using GENECUBE Mycoplasma were performed. Results. The system reproducibly identified all synthetic oligonucleotides associated with high-level macrolide resistance. Detection errors were only observed for A2067G (in 2 of the 10 measurements). The point mutation in 23S rRNA was detected in 67 (26.9 %) of 249 confirmed M. pneumoniae -positive clinical samples. The mutations at positions 2063, 2064 and 2617 were observed in 65 (97.0 %), 2 (3.0 %) and 0 (0.0 %) of the 67 samples, respectively. The mutations at positions 2063 and 2064 were A2063G and A2064G, respectively. The results from mutant typing using GENECUBE Mycoplasma were in full agreement with the results from sequence-based typing. Conclusion. GENECUBE Mycoplasma is a reliable test for the identification of clinically significant macrolide-resistant M. pneumoniae .

A subset analysis of the CA031 trial showed significant improvement in the overall response rate after administration of carboplatin plus weekly albumin-bound paclitaxel compared to carboplatin plus paclitaxel for squamous cell carcinoma of the lung (SQ). We conducted this phase II study to compare carboplatin plus weekly albumin-bound paclitaxel (CnP) to cisplatin plus gemcitabine (CG), a standard regimen for SQ. Chemotherapy-naive patients with SQ were randomly assigned to receive cisplatin (80 mg/m2) on day 1 plus gemcitabine (1000 mg/m2) on days 1 and 8 every 3 weeks or carboplatin (area under the curve: 6 mg/mL/min) on day 1 plus nab-paclitaxel (75 mg/m2) on days 1, 8, and 15 every 3 weeks. The primary endpoint was overall response rate. The secondary endpoints were progression-free survival, overall survival, disease control rate, and toxicity. Between June 2013 and October 2018, 71 patients were enrolled and assigned to either the CG arm (n = 35) or the CnP arm (n = 36) of the study. The overall response rate was 43% [95% confidence interval (CI) 27.3–58.5] in the CG arm and 47% (95% CI 31.7–62.7) in the CnP arm. Although drug combination efficacies did not differ, there were differences in toxicity: hematologic toxicities (leukopenia, neutropenia, and thrombocytopenia) were found mostly in the CG arm, whereas anemia and sensory neuropathy were more common in the CnP arm. CnP had similar response as CG despite being a carboplatin-based regimen and toxicities differed between arms. Regarding ORR, CnP was comparable to CG for SQ.

Background Anti-programmed cell death 1 antibody is a standard therapy for advanced non-small cell lung cancer (NSCLC). However, immune-related adverse events (irAEs), such as skin reactions, are frequently observed. Although skin reactions are associated with clinical efficacy in melanoma, this association in advanced NSCLC and predictors of irAEs remain unclear. Accordingly, this study identified potential correlations of skin reactions with clinical efficacy and clinical predictors of development of skin reactions. Subjects, Materials, and Methods We retrospectively surveyed patients with advanced NSCLC who received nivolumab or pembrolizumab monotherapy at Sendai Kousei Hospital (n = 155) during January 2016 to April 2018. Treatment efficacy was evaluated in patients with and without skin reactions, and associated predictive markers were determined. A 6-week landmark analysis was conducted to assess the clinical benefit of early skin reactions. Results Skin reactions were observed in 51 patients with a median time to onset of 6.4 weeks. The overall response rate (ORR) was significantly higher in patients with skin reactions (57% vs. 19%, p < .001). Median progression-free survival (PFS) durations of 12.9 and 3.5 months and overall survival durations of not reached and 11.4 months were observed in patients with and without skin reactions, respectively. In the 6-week landmark analysis, the ORR was significantly higher in patients with skin reactions, and skin reactions were significantly associated with increased PFS. A multivariate analysis identified pre-existing rheumatoid factor (RF) as an independent predictor of skin reactions. Conclusion Skin reactions appeared beneficial in patients treated with nivolumab/pembrolizumab for advanced NSCLC and could be predicted by pre-existing RF. Further large-scale validations studies are warranted.

Purpose This phase II study was designed to evaluate the efficacy and safety of S-1 combined with weekly irinotecan as second- or third-line treatment for patients with advanced or recurrent squamous cell lung cancer. Methods Patients received oral S-1 on days 1–14 at 80 mg/day for patients with a body surface area of 2, 100 mg/day for patients with a body surface area of 1.25–1.5 m2, and 120 mg/day for patients with a body surface area of > 1.5 m2 and irinotecan (70 mg/m2) on days 1 and 8 every 3 weeks. The primary endpoint was overall response rate, and the secondary endpoints were progression-free survival, overall survival, and the frequency and the degree of adverse effects. The trial was registered in the University Hospital Medical Information Network Clinical Trials Registry, number UMIN000006065. Results Between September 2011 and December 2014, 30 patients were enrolled in this study. The overall response rate was 6.7% (95% CI 0.8–22.1) and the disease control rate was 73.3%. The median progression-free survival was 3.0 months (95% CI 2.5–3.4) and median overall survival was 10.5 months (95% CI 5.6–13.7). Grade 3 or 4 treatment-related toxicities were reported in ≥ 10% of patients including leukopenia (21%), neutropenia (21%), anemia (17%), anorexia (10%), and hypokalemia (10%). Conclusion Adding weekly irinotecan to S-1 did not show the expected effect though toxicities were manageable.

9030 Background: Immuno-checkpoint inhibitor (ICI) monotherapy is a standard second-line treatment for non-small-cell lung cancer (NSCLC). Addition of a cytotoxic agent to ICI may enhance the benefits. Methods: This multi-institutional open-label randomized phase II/III study compared the arm A consisting of nivolumab (NIV) monotherapy and arm B consisting of NIV + docetaxel (DTX) for patients with previously treated ICI-naïve NSCLC, prestratified by PS/histological types/sex/driver-mutations. The primary endpoint was superiority of arm B in OS in the phase III part. Assuming a HR of 0.75 for OS with the estimated mOS of arm A/B as 10.5/14.0 mo, a total 350 patients would be required to provide 80% power at a one-sided α of significance being 0.05. It was started at Nov. 2017, however, the patients’ accrual was discontinued due to the approval of ICI in the first-line setting in late 2018. Eventually, a total of 131 patients were enrolled for analysis. Results: 128 patients (64 in each arm) were eligible and included in full analysis set (FAS), and the patients’ demographics were well-balanced in each arm. The mOS was 14.7 mo (95%CI, 11.4-18.7) in arm A, and 23.1 mo (95%CI, 16.7-NR) in arm B. The HR of OS was 0.63 (90%CI, 0.42-0.95; p = 0.0310). The mPFS was 3.1 mo (95%CI, 2.0-3.9) and 6.7 mo (95%CI, 3.8-9.4) in arm A and B, respectively. The HR for PFS was 0.58 (95%CI, 0.39-0.88; p = 0.0095). The ORR was 14.0% (95%CI, 6.3-25.8) in arm A, and 41.8% (95%CI, 28.7-55.9) in arm B, with a statistical significance (p = 0.0014). Subgroup analyses for OS disclosed that the HRs favored arm B over arm A across all prespecified subgroups. The mOS of EGFR-mutant subgroup also showed better tendency in arm B than A (11.0 mo in arm A; 95%CI, 3.5-14.0; vs 20.6 mo in B; 95%CI, 5.8-NR; HR 0.45; 95%CI, 0.17-1.17). The hematological toxicity and gastrointestinal adverse events were more common in arm B than in A. Six (9.4%) in arm A and 25 patients (39.1%) in arm B discontinued protocol treatment due to adverse events. Overall, two treatment-related deaths were observed; one from pneumonitis in arm A, and one from myocarditis in arm B. Conclusions: Although the resulting statistical power was limited because of reduced sample size, the addition of DTX to NIV in the second-line NSCLC therapy significantly improved OS, PFS, and ORR, despite slightly elevated risk of toxicity. This is the first randomized clinical trial that confirmed significant survival benefit of ICI + chemotherapy over ICI alone in any cancer type. Clinical trial information: UMIN000021813.

Background: In NEJ026, a phase III trial comparing bevacizumab plus erlotinib (BE) to erlotinib alone (E) for advanced EGFR-mutant non-small-cell lung cancer (NSCLC), we demonstrated that the progression-free survival (PFS) of BE was significantly superior to E. Here, we report the results from the analysis of final overall survival (OS) time from enrolment to progressive disease during second-line treatment (PFS2), and quality of life (QoL). Methods: Chemotherapy-naive advanced EGFR-mutant NSCLC patients were randomly assigned to receive either erlotinib 150 mg/day plus bevacizumab 15 mg/kg once every 21 days, or erlotinib alone. Kaplan-Meier curves were drawn for OS and PFS2 using a stratified log-rank test. QoL was assessed by determining the period that elapsed between enrolment to confirmation of a minimally important difference (MID) using the European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ)-C30. Findings: The 224 patients were assigned to BE (n=112) and E (n=112). For the OS analysis, the data cut-off date was 30 November 2019. Median follow up time was 39·2 months. Median OS was 50·7 months (95% CI 37·3–not reached) with BE and 46·2 months (95% CI 38·2–not reached) with E (hazard ratio 1·007; 95% CI 0·681–1·490). The median PFS2 was 28·6 months (95% CI 22·1–35·9) with BE and 24·3 months (95% CI 20·4–29·1) with E (hazard ratio, 0·795; 95% CI 0·578–1·094). Median time between enrolment and confirmation of MID was 6·0 months (95% CI 5·2–11·3) with BE and 8·3 months (95% CI 5·7–13·9) with E. Interpretation: In NEJ026, both BE and E were associated with prolonged OS, but addition of bevacizumab to the erlotinib regimen was not beneficial. Trial Registration: The trial is registered with the University Hospital Medical Information Network Clinical Trials Registry, number UMIN000017069. Funding Statement: Chugai Pharmaceutical. Declaration of Interests: TF reports personal fees from Chugai Pharma., during the conduct of the study; personal fees from Astrazeneca, personal fees from Boehringer Ingelheim, outside the submitted work. HS reports grants from Chugai Pharmaceutical, grants from AstraZeneca, personal fees from Ono Pharmaceutical, personal fees from Nippon Boehringer Ingelheim, grants from MSD, personal fees from Novartis Pharma, outside the submitted work. NF reports personal fees from AstraZeneca, personal fees from Chugai, personal fees from Boehringer Ingelheim, personal fees from Eli Lilly, personal fees from Bristol-Myers Squibb, personal fees from Novartis, personal fees from Taiho, personal fees from Kyowa Kirin, personal fees from MSD, personal fees from Pfizer, outside the submitted work. SS reports personal fees from Chugai Pharma, personal fees from AstraZeneca, personal fees from Nippon Boehringer Ingelheim, personal fees from MSD, personal fees from Bristol-Myers Squibb, personal fees from Ono Pharmaceutical, personal fees from Pfizer, personal fees from Taiho Pharmaceutical, personal fees from Eli Lilly and Company, personal fees from Novartis, personal fees from Kyowa Hakko Kirin, personal fees from Yakult Honsha, outside the submitted work. SI reports grants and personal fees from ONO PHARMACEUTICAL CO., LTD., personal fees from Chugai Pharmaceutical Co., Ltd., personal fees from AstraZeneca K.K., personal fees from MSD K.K, personal fees from Bristol-Myers Squibb K.K., personal fees from Eli Lilly Japan K.K., personal fees from Taiho Pharmaceutical Co., Ltd., personal fees from DAIICHI SANKYO COMPANY, LIMITED., outside the submitted work. OY reports personal fees from Ono Pharmaceutical Co., Ltd., personal fees from Bristol-Myers Squibb, personal fees from Chugai Pharmaceutical Co., Ltd., personal fees from AstraZeneca, personal fees from Eli Lilly Japan, outside the submitted work. MO reports grants from Chugai Pharmaceutical Co., Ltd., during the conduct of the study. MS reports grants and personal fees from Chugai Pharmaceutical., during the conduct of the study. KA reports personal fees from Ono Pharmaceutical, personal fees from Chugai Pharmaceutical, personal fees from Astra Zeneca, personal fees from MSD Oncology, personal fees from Bristorl Myers Squibb, outside the submitted work. YuT reports personal fees from Chugai Pharmaceuticals Co Ltd, personal fees from AstraZeneca Co Ltd, personal fees from Daiichi Sankyo Co Ltd, outside the submitted work. YF reports personal fees from Liliy, personal fees from Chugai Pharma, personal fees from AstraZeneca, personal fees from Bristol-Myers Squibb Company, outside the submitted work. SW reports grants and personal fees from AstraZeneca, personal fees from Chugai Pharma, personal fees from Ono Pharmaceutical, personal fees from Bristol-Myers, grants and personal fees from Boehringer Ingelheim, personal fees from Eli Lilly, personal fees from MSD, personal fees from Taiho Pharmaceutical, personal fees from Pfizer, personal fees from Novartis, personal fees from Daiichi Sankyo, outside the submitted work. KH reports personal fees from Astra Zeneca, personal fees from Chugai Pharmaceutical, grants and personal fees from Taiho Pharmaceutical, grants and personal fees from Ono Pharma, personal fees from Boehringer-ingelheim, personal fees from Novartis, personal fees from Kyorin pharmaceutical, personal fees from Bristol Myers Squibb, grants from MSD, outside the submitted work. In addition, KH has a patent EGFR mutation test licensed to LSI medience. SM reports personal fees from AstraZeneca K.K, personal fees from Bristol-Myers Squibb Company, personal fees from Chugai Pharmaceutical Co. Ltd, personal fees from Eli Lilly Japan K.K, personal fees from MSD K.K, personal fees from Pfizer Japan Inc, personal fees from Taiho Pharmaceutical Co. Ltd, personal fees from Ono Pharmaceutical Co. Ltd., outside the submitted work. KK reports personal fees from AstraZeneca, personal fees from Bristol-Myers Squibb Japan, personal fees from Ono Pharmaceutical, personal fees from Boehringer Ingelheim, personal fees from Taiho Pharmaceutical Company, outside the submitted work. MMa reports grants and personal fees from chugai pharm., during the conduct of the study; personal fees from chugai pharm., personal fees from astrazeneca, personal fees from boehringer ingelheim, personal fees from Lilly, outside the submitted work. YK, KW, YoT, KY, IN, FK, HN, GA, MMi, and TN declare no competing interests. Ethics Approval Statement: The study was done in accordance with the Helsinki Declaration and Good Clinical Practice Guidelines. The study protocol was reviewed and approved by the ethical committee of the Non-Profit Organization MINS Institutional Review Board and by the local institutional review boards of the participating institutions. Written informed consent was obtained from all enrolled patients.

Recently, a new rapid assay for the detection of tcdB gene of Clostridioides difficile was developed using the GENECUBE. The assay can directly detect the tcdB gene from stool samples without a purification in approximately 35 minutes with a few minutes of preparation process. We performed a prospective comparative study of the performance of the assay at eight institutions in Japan. Fresh residual stool samples (Bristol stool scale ≥5) were used and comparisons were performed with the BD MAX Cdiff assay and toxigenic cultures. For the evaluation of 383 stool samples compared with the BD MAX Cdiff assay, the sensitivity, and specificity of the two assays was 99.0% (379/383), 98.1% (52/53), 99.1% (327/330), respectively. In the comparison with toxigenic culture, the total, sensitivity, and specificity were 96.6% (370/383), 85.0% (51/60), and 98.8% (319/323), respectively. The current investigation indicated the GENECUBE Clostridioides difficile assay has equivalent performance with the BD MAX Cdiff assay for the detection of tcdB gene of C. difficile.

Background/aim Promising reports have described the combination of first-generation epidermal growth factor receptor tyrosine-kinase inhibitors (EGFR-TKIs) with carboplatin plus pemetrexed or bevacizumab. However, no analysis of afatinib with platinum-doublet chemotherapies has been performed. Patients and methods We evaluated the safety and antitumor efficacy of afatinib combined with carboplatin and pemetrexed in EGFR-mutated non-small-cell lung cancer (NSCLC) patients who progressed during first-generation EGFR-TKIs. Results Ten patients received 20 or 30 mg/day afatinib with carboplatin (area under the curve, 5) and pemetrexed (500 mg/m2). Dose-limiting toxicities included delay of afatinib ≥14 days, grade 3 diarrhea, grade 3 hypokalemia, grade 3 serum amylase increase and grade 4 thrombocytopenia. The recommended dose of afatinib was 20 mg/day in this combination therapy. Overall response rate was 30% and median progression-free survival was 13.7 months. Conclusion This is the first study to investigate the combination of afatinib, carboplatin and pemetrexed. At the recommended dose, this combination was well tolerated and had a good clinical efficacy.

Although anti-PD-1/PD-L1 monotherapy has achieved clinical success in non-small cell lung cancer (NSCLC), definitive predictive biomarkers remain to be elucidated. In this study, we performed whole-transcriptome sequencing of pretreatment tumor tissue samples and pretreatment and on-treatment whole blood samples (WB) samples obtained from a clinically annotated cohort of NSCLC patients (n = 40) treated with nivolumab (anti-PD-1) monotherapy. Using a single-sample gene set enrichment scoring method, we found that the tumors of responders with lung adenocarcinoma (LUAD, n = 20) are inherently immunogenic to promote antitumor immunity, whereas those with lung squamous cell carcinoma (LUSC, n = 18) have a less immunosuppressive tumor microenvironment. These findings suggested that nivolumab may function as a molecular targeted agent in LUAD and as an immunomodulating agent in LUSC. In addition, our study explains why the reliability of PD-L1 expression on tumor cells as a predictive biomarker for the response to nivolumab monotherapy is quite different between LUAD and LUSC.

Early detection of the family Chlamydiaceae as pathogens is essential worldwide for the rapid and sufficient management of atypical pneumonia. GENECUBE (TOYOBO) is a novel fully automated gene analyzer capable of amplifying and detecting target DNAs within 50 min. In this study, we developed a new PCR assay with a specific quenching probe (PCR-QC assay) for rapidly distinguishing between Chlamydia pneumoniae (CPN) and Chlamydia psittaci (CPS). The PCR-QC assay enabled us to precisely and simultaneously detect the 2 different types of DNA fragments even in a mixed sample by identifying unique melting temperatures. Next, we examined a total of 300 frozen samples from patients with respiratory tract infection using the PCR-QC assay and the cell culture method as the gold standard. Kappa index for agreement between the PCR-QC assay and the culture method was 0.43 (95% confidential interval (CI): 0.08–0.78). The sensitivity and specificity of the PCR-QC assay were 36.3% (4/11; 95% CI: 10.9–69.2%)) and 99.0% (286/289; 95% CI: 97.0–99.8%), respectively. The samples positive for CPN ( n = 13) or CPS (n = 1) by either method were also examined by a conventional PCR TaqMan assay, which produced the same results as those from the PCR-QC assay. Furthermore, the PCR-QC assay using GENECUBE shortened the full detection time for CPN or CPS (within 50 min vs. more than 2 to 3 h) compared with conventional PCR TaqMan assays. Therefore, the new PCR-QC assay system equipped with GENECUBE is useful for rapidly detecting CPN or CPS pathogens in clinical laboratory, and may improve the management of atypical pneumonia.

Introduction: Immune checkpoint inhibitors (ICIs) can lead to immune-related adverse events (irAEs). A correlation between the development of irAEs and efficacy has been suggested; however, it is unclear whether there is a relationship between programmed death ligand 1 (PD-L1) expression and the development of these events. Methods: We performed a retrospective study of advanced or metastatic non-small cell lung cancer (NSCLC) patients who were treated with pembrolizumab monotherapy at our institution between May 2015 and April 2018 (n = 44). Patients were categorized into two groups, specifically those with irAEs (irAE group) or without (non-irAE group), and we evaluated the objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS). Predictors of irAEs were examined by multivariate analysis. Results: irAEs of any grade occurred in 31 (70.5%) patients. The median PFS was 10.9 months in the irAE group versus 3.7 months in the non-irAE group (P < 0.001). ORR and DCR were also higher in the irAE group than in the non-irAE group. Furthermore, high PD-L1 expression (≥50%) was a predictive factor of irAE based on logistic regression (P = 0.004). Conclusions: In patients with advanced NSCLC treated with pembrolizumab monotherapy, ORR, DCR, and PFS were significantly better in the irAE group than in the non-irAE group. High PD-L1 expression, at the time of pretreatment, was identified as an independent predictor of irAE development. We believe that more careful management of irAEs for individuals with high PD-L1 expression is needed to improve clinical benefits. Further, PD-L1 expression might be useful for ICI risk management.

IMPORTANCE: Administration of anti–programmed cell death protein 1 (anti–PD-1) is now standard therapy in advanced non–small cell lung cancer (NSCLC). However, immune checkpoint inhibitors, including anti–PD-1, have not been assessed in patients with subclinical disease with advanced NSCLC, and no useful clinical biomarkers have been associated with immune-related adverse events (irAEs) among these patients treated with anti–PD-1. OBJECTIVE: To assess the safety and efficacy of anti–PD-1 treatment in patients with subclinical disease with advanced NSCLC and with or without preexisting autoimmune markers, including rheumatoid factor, antinuclear antibody, antithyroglobulin, and antithyroid peroxidase; and to assess potential clinical biomarkers that may be meaningfully and conveniently associated with clinical benefit or with irAEs following anti–PD-1 treatment. DESIGN, SETTING, AND PARTICIPANTS: This medical records analysis retrospectively evaluated 137 patients who received nivolumab or pembrolizumab monotherapy at Sendai Kousei Hospital in Japan between January 2016 and January 2018. Treatment efficacy and irAEs were evaluated along with candidate factors that may be associated with irAEs. EXPOSURES: Absence or presence of specific autoimmune markers and antibodies before treatment. MAIN OUTCOMES AND MEASURES: Preexisting antibodies and autoimmune markers, progression-free survival (PFS), and irAEs. RESULTS: Of 137 patients with advanced NSCLC, 105 were men, the median age was 68 (range, 36-88) years, 99 underwent nivolumab monotherapy, 38 underwent pembrolizumab monotherapy, and 134 had an Eastern Cooperative Oncology Group performance status of 0 or 1. The median PFS was 6.5 (95% CI, 4.4-12.9) months among patients with examined preexisting antibodies and 3.5 (95% CI, 2.4-4.1) months among patients without, suggesting significantly better prognosis in the former. The hazard ratio for disease progression or death in the presence of the examined preexisting antibodies was 0.53 (95% CI, 0.36-0.79; P = .002). The PFS was significantly longer among patients with any preexisting antibodies than among those without. The examined preexisting antibodies (48 patients [73%]) and rheumatoid factor (26 patients [39%]) were more common among patients who developed irAEs. Multivariate analysis indicated that the presence of the examined preexisting antibodies was independently associated with irAEs (odds ratio, 3.25; 95% CI, 1.59-6.65; P = .001). Skin reactions were more frequent among patients with preexisting rheumatoid factor (47% vs 24%, P = .02), whereas thyroid dysfunction was more frequent among patients with preexisting antithyroid antibodies (20% vs 1%, P

Rapid identification of causative agents from positive blood culture media is a prerequisite for the timely targeted treatment of patients with sepsis. The GENECUBE (TOYOBO Co., Ltd.) is a novel, fully-automated gene analyzer that can purify DNAs and amplify target DNAs. In this study, we evaluated the ability of two newly developed GENECUBE assays to directly detect the nuc and mecA genes in blood culture medium; nuc is specific to Staphylococcus aureus, and mecA indicates methicillin resistance. We examined 263 positive blood culture samples taken at three hospitals from patients suspected of having staphylococcal bacteremia. The results were then compared with those obtained using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, antimicrobial susceptibility testing (Microscan system or Dry-plate EIKEN), and sequencing analysis. The GENECUBE assays had sensitivity and specificity of 100% in detecting both S. aureus and methicillin resistance in positive blood culture. The turnaround time of the examination was evaluated for 36 positive blood culture samples. The time between the initiation of incubation and completion of the GENECUBE examination was 23 h (interquartile range: IQR 21–37 h); the time between reporting of Gram stain examination and completion of the GENECUBE examination was 52 min (IQR 48–62 min). These findings show that the GENECUBE assays significantly reduce the assay time with no loss of sensitivity or specificity.

Objectives In the past two decades several antineoplastic agents have been approved for the treatment of advanced non-small-cell lung cancer (NSCLC), and the management of these patients has drastically changed. However, there is limited information regarding the impact of these advances on patient survival in clinical practice. Materials and methods We analyzed the survival of patients with stage IV NSCLC who received any treatment in the Cancer Institute Hospital of the Japanese Foundation for Cancer Research (JFCR) between January 1, 1995 and March 1, 2017. A total of 1,547 consecutive patients were included in this case series. In this analysis, five diagnostic periods were evaluated: 1995–1999 (period A), 2000–2004 (period B), 2005–2009 (period C), 2010–2014 (period D), and 2015–2017 (period E). We compared overall survival (OS) between the periods before and after propensity score matching (PSM) and in patients with EGFR mutation, with ALK fusion gene, or without driver mutation. Results In the past two decades the OS of patients with stage IV NSCLC improved. The median OSs for periods A, B, C, D, and E were 9.0, 11.0, 13.7, 17.9 months, and not reached, respectively. After PSM with known baseline characteristics, the trend of improvement in OS was similar. However, the OS of patients with EGFR mutation or ALK fusion gene did not improve between periods, despite the availability of several tyrosine kinase inhibitors in Japan. The OS of patients without a driver mutation was slightly longer in the period E. Conclusion The introduction of new classes of drugs has significantly improved the survival of patients with stage IV NSCLC. However, the approval of similar types of drugs may not be associated with further improvement in survival.

Nucleic acid amplification tests (NAATs) are considered as one of critical diagnostic methods on Chlamydia trachomatis and Neisseria gonorrhoeae infections due to their high sensitivity and accuracy. However, conventional NAATs required 2-6 hours to complete the measurements including extraction, amplification, and detection of the target nucleic acids. To reduce the time, we evaluated the clinical significance of the rapid NAAT using GENECUBE (TOYOBO CO., LTD.) which can complete the measurement within 1 hour. We compared the performance of GENECUBE with those of TMA method (APTIMA" Combo2 chlamydia/ gonorrhoeae, Hologic Japan, Inc.) and lateral flow immunochromatographic assay (Clearview Chlamydia, Clearview gonorrhoeae, Alere Medical Co., Ltd.) by detecting specimens from 96 cervical swabs. The overall agreement results between GENECUBE and TMA were 95.8% and 100% for C. trachomatis and N. gonorrhoeae, respectively. The results suggested that GENECUBE showed equivalent sensitivity and specificity of TMA. Indeed, more than half of the positive samples in NAATs were measured as negative in the lateral flow. The lateral flow is known as a rapid assay, however the results revealed its poor sensitivity. We think rapid NAATs using GENECUBE on C. trachomatis and N. gonorrhoeae can be one of the methods, which realize rapid tests with high sensitivity and accuracy.

Background Immune-related adverse events (irAEs) are frequently observed with nivolumab monotherapy. This study aimed to evaluate whether the development of irAEs correlates with treatment response in advanced non-small-cell lung cancer (NSCLC). Patients and Methods We conducted a retrospective study of patients who received nivolumab monotherapy at Sendai Kousei Hospital (n = 70). The patients were categorized into two groups based on the incidence of irAEs: those with irAEs (irAE group) or those without (non-irAE group). Treatment efficacy was evaluated in each group. The patients were further categorized into responders and nonresponders, and predictive factors of treatment response were determined. Results The objective response rate was 57% in the irAE group versus 12% in the non-irAE group. Median progression-free survival was 12.0 months in the irAE versus 3.6 months in the non-irAE group. The incidence of both irAEs and pre-existing antithyroid antibody was significantly higher in responders than in nonresponders. Multivariate analysis identified incidence of irAEs and pre-existing antithyroid antibody as an independent predictor of treatment response. Conclusion Objective response rate and progression-free survival were significantly better in the irAE than in the non-irAE group in patients with advanced NSCLC treated with nivolumab monotherapy. The development of irAEs was associated with clinical efficacy, and the presence of pre-existing antithyroid antibody might be correlated with treatment response to nivolumab monotherapy. Implications for Practice Immune-related adverse events (irAEs) are frequently observed with nivolumab monotherapy. This study evaluted whether the development of irAEs correlates with treatment response in advanced non-small-cell lung cancer. Results showed that the objective response rate and progression-free survival were significantly better in the patients who developed irAEs than in the patients who did not develop irAEs, and the incidence of irAEs and positivity for antithyroid antibody at pretreatment were independent predictors of treatment response of nivolumab monotherapy. Therefore, the development of irAEs predicts clinical benefit and suggests that cautious management of irAEs can lead to achieving maximum clinical benefit from nivolumab monotherapy.

Background Atezolizumab, an anti-programmed death-ligand 1 (PD-L1) agent, is effective and well tolerated in the first-line treatment of Extensive-Stage Small Cell Lung Cancer (ES-SCLC). We assessed its efficacy and safety in Japanese patients through subgroup analyses of the phase 3 IMpower133 trial (NCT02763579). Methods IMpower133 is a Phase I/III, multicenter, double-blinded, placebo-controlled randomized trial evaluating atezolizumab plus carboplatin and etoposide in chemotherapy-naive ES-SCLC patients. Patients were randomly assigned in a 1:1 ratio to receive carboplatin and etoposide with either atezolizumab or placebo for four 21-day cycles (induction phase), followed by a maintenance phase during which they received either atezolizumab or placebo until they had unacceptable toxicity, disease progression according to Response Evaluation Criteria in Solid Tumors, version 1.1, or no additional clinical benefit. The two primary endpoints were investigator-assessed progression-free survival and overall survival in the intention-to-treat population. Results Of the 403 patients randomized in the IMpower133 trial, 42 patients were enrolled from Japanese centers. In Japanese patients from the ITT population, median PFS in the atezolizumab group (n = 20) was longer than the placebo group (n = 22; 4.5 months [95% CI, 4.2-8.1] vs 4.0 months [95% CI, 2.9-5.6], respectively; HR 0.47 [95% CI, 0.23-0.96]), and median OS in the atezolizumab group was longer than the placebo group (14.6 months [95% CI, 11.8-17.8] vs 11.9 months [95% CI, 8.4-15.8], respectively; HR 0.72 [95% CI, 0.31-1.67]). The atezolizumab regimen was generally well tolerated, with no treatment-related deaths. Conclusion The addition of atezolizumab to carboplatin and etoposide was effective and well tolerated in Japanese patients with ES-SCLC. Results are consistent with the primary analysis of IMpower133 trial.

Background Although anti-PD-1 antibodies are the most promising agents in advanced non-small cell lung cancer (NSCLC), no definitive biomarkers of efficacy exist. We developed a novel assay for peripheral blood mononuclear cell (PBMC) biomarker using the prediction formula consisting of CD62L-downregulated (CD62Llow) CD4+T cells and CD25+Foxp3+CD4+T cells. This study aimed to validate it. Methods This prospective multicenter phase II study included patients with treated advanced or metastatic NSCLC. After registration and PBMC biomarker analysis, they were classified into responder (RT) or non-responder (NRT) type. Nivolumab was administered every two weeks. The primary endpoint was disease control rate (DCR) at nine weeks after nivolumab treatment in RT patients. Desired and threshold DCR were set at 80% and 60%, respectively. Secondary endpoints were objective response rate (ORR), time to treatment failure, progression-free survival (PFS), overall survival, safety and tolerability, comparison with NRT patients, and PBMC biomarker quality improvement. Results Of the 96 enrolled patients, 95 were eligible for PBMC analysis: 3 were unanalyzable, and 92 were analyzed; however, 40 had a minimal number of live cells. We excluded 19 patients who did not receive nivolumab in NRT and 1 with indeterminable treatment effect at nine weeks, and 72 patients comprised the per protocol set (PPS), of which 43 were RT and 29 NRT. The DCR and ORR in RT patients were 65.1% (95% confidence interval [CI], 50.9-79.4%) and 14.0% (95% CI, 3.6-24.3%), respectively. The PFS in RT patients was 113 days (95% CI, 65-158). As a subset analysis, we examined 45 patients (25 RT and 20 NRT) excluding those with ≥50% dead cell ratio in lymphocyte culture. The DCR was 80.0% (95%CI, 64.3-95.7) in RT and 50.0% (95% CI, 28.1-71.9) in NRT (chi-square test, p = 0.034). Conclusions In alive PBMC analysis, DCR was better in the RT than in the NRT patients. This PBMC biomarker using the ratio of CD62LlowCD4+T cells to CD25+Foxp3+CD4+T cells might be promising for predicting nivolumab efficacy. Clinical trial identification UMIN ID: UMIN000028468. Legal entity responsible for the study North East Japan Study Group (NEJSG). Funding Ono Pharmaceutical Co., Ltd., Bristol-Myers Squibb K.K. Disclosure O. Yamaguchi: Research grant / Funding (institution): Nihon Medi-Physics Co., Ltd.; Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: Ono Pharmaceutical; Speaker Bureau / Expert testimony: Bristol-Myers Squibb. T. Kozuki: Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self): Nippon Beohringer Ingelheim Co.; Honoraria (self), Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self), Research grant / Funding (institution): Chugai Pharmaceutical Co.; Honoraria (self): Kyowa-Hakko Kirin; Honoraria (self), Research grant / Funding (institution): Eli Lilly Japan; Research grant / Funding (institution): Merck Biopharm; Honoraria (self): MSD; Honoraria (self): Ono Pharmaceutical Co.; Honoraria (self): Pfizer; Honoraria (self): Taiho Pharmaceutical Co. N. Furuya: Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Lilly; Honoraria (self): Chugai Pharma ; Honoraria (self): AstraZeneca; Honoraria (self): Pfizer; Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Ono Pharmaceutical. T. Yamada: Research grant / Funding (self): Ono Pharmaceutical Co., Ltd.; Research grant / Funding (self): Boehringer Ingelheim Japan Inc.; Research grant / Funding (self): Takeda Pharmaceutical Co. Ltd.; Research grant / Funding (self): Chugai Pharmaceutical Co., Ltd. R. Ko: Honoraria (self): Ono Pharmaceutical Co., Ltd. T. Harada: Honoraria (institution): Boehringer Ingelheim; Honoraria (institution): Hisamitsu Pharmaceutical Co., Inc; Honoraria (institution): GlaxoSmithKleine K.K. M. Seike: Honoraria (self), Research grant / Funding (institution): Ono Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Bristol-Myers Squibb. K. Yoshimura: Honoraria (self): Chugai Pharma. K. Kobayashi: Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: Boehringer Ingelheim; Speaker Bureau / Expert testimony: Taiho Pharmaceutical Company; Speaker Bureau / Expert testimony: Ono Pharmaceutical Company. H. Kagamu: Honoraria (self), Research grant / Funding (institution): Ono Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Taiho Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Chugai Pharmaceutical; Honoraria (self): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Boehringer Ingelheim; Honoraria (self), Research grant / Funding (institution): Eli Lilly Japan. All other authors have declared no conflicts of interest.

In patients with non-small-cell lung cancer harboring an epithelial growth factor receptor (EGFR) active mutation, central nervous system progression after a response to EGFR tyrosine kinase inhibitors is frequent. Central nervous system metastasis, especially leptomeningeal carcinomatosis (LMC), is a serious complication and no standard treatment has been established for LMC. Here, we report two cases in which the addition of bevacizumab to erlotinib enhanced the efficacy against LMC; as a result, radiographic abnormalities decreased markedly and symptoms were well controlled. This combination treatment may be useful to treat LMC in patients with EGFR-positive non-small-cell lung cancer.

Background The subset analysis of CA031 trial showed a significant improvement of overall response rate (ORR) for carboplatin (CBDCA) plus weekly nab-paclitaxel (CnP) versus CBDCA plus paclitaxel in patients (pts) with squamous cell histology (41% vs 24%). We conducted a phase II study comparing CnP to cisplatin plus gemcitabine (CG), one of the standard regimens in pts with squamous cell lung cancer (SCC). Methods Chemo-naive stage IIIB/IV or postoperative recurrent SCC pts were randomly assigned to receive either cisplatin (80 mg/m2) on day 1 plus gemcitabine (1000 mg/m2) on days 1, 8 every 3 weeks or CBDCA (AUC 6 mg/ml/min) on day 1 plus nab-PTX (75 mg/m2) on days 1, 8, 15 every 3 weeks. The primary endpoint was ORR. Secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and toxicity. Assuming that an ORR of 40% in eligible pts indicates potential usefulness and ORR of 20% is the lower limit of interest, the estimated accrual was 32 pts in each arm. Allowing for dropouts, the accrual goal was determined to be 35 pts in each arm (alpha, 0.05; beta, 0.20). Results Between June 2013 and October 2018, 71 pts were enrolled and assigned to CG arm (n = 35) and CnP arm (n = 36). The median follow-up time was 10.2 months. At data cutoff, ORR was 40% (95% confidence interval [CI]: 24.5-55.5) in CG arm and 47% (95%CI: 31.7-62.7) in CnP arm. DCR was 74% in CG arm and 80% in CnP arm. Median PFS was 4.6 months in CG arm and 4.3 months in CnP arm. Median OS was 10.9 months in CG arm and 10.0 months in CnP arm. Of the grade 3 or higher adverse events, anemia was more common in CnP arm (CG, 17% and CnP, 53%). There was one treatment-related death in CG arm and no treatment-related death in CnP arm. Conclusions In this study, both CnP and CG arms met the primary endpoint. Carboplatin-based CnP regimen was likely to be equivalent to CG for SCC.