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Background: Efficacy of necitumumab [recombinant human monoclonal antibody that blocks the ligand binding epidermal growth factor receptor (EGFR)] in patients with squamous (SQ) non-small-cell lung cancer (NSCLC) has been confirmed in two randomized clinical trials (SQUIRE and JFCM). This study evaluated the association between efficacy and initial skin toxicity with necitumumab treatment by analyzing pooled data from two clinical trials (SQUIRE and JFCM)., Materials and Methods: Data of 635 patients with SQ-NSCLC (intent-to-treat population) treated with necitumumab plus gemcitabine and cisplatin (N + GC) were pooled from two clinical trials (SQUIRE and JFCM). The relationship between skin toxicities developed by the end of the second cycle and efficacy was evaluated. Efficacy endpoints included overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Univariate and multivariate analyses were carried out for these endpoints., Results: OS and ORR were associated with skin toxicity, whereas PFS was not. Patients with grade ≥2 or grade 1 skin toxicity had significantly longer OS compared to patients without skin toxicity (grade 0) in the N + GC group [median = 15.0 (grade ≥2); 12.7 (grade 1); 9.4 (grade 0) months; hazard ratio (HR) = 0.51 (grade ≥2 to grade 0); 95% confidence interval (CI) 0.40-0.64, P < 0.001 and HR = 0.64 (grade 1 to grade 0); 95% CI 0.52-0.80, P < 0.001]. In multivariate analysis, OS was significantly associated with skin toxicity., Conclusions: A significant association was found between necitumumab-induced skin toxicity and efficacy. These results are consistent with the previously reported association between other EGFR inhibitors-induced skin toxicity and efficacy., Competing Interests: Disclosure SW reports receiving personal fees from Novartis Pharma, Chugai Pharmaceutical, Boehringer Ingelheim, Ono Pharmaceutical, Taiho Pharmaceutical, AstraZeneca, Bristol-Myers Squibb, MSD, and Daiichi Sankyo. HY reports receiving personal fees from Delta Fly Pharma, Chugai Pharmaceutical, MSD, AstraZeneca, Boehringer Ingelheim, Taiho Pharmaceutical, Ono Pharmaceutical, Bristol-Myers Squibb, Novartis Pharma, Kyowa Kirin, Nippon Kayaku, Eli Lilly, Otsuka Pharmaceutical, Daiichi Sankyo, Amgen, Pfizer, and Nipro Pharma. HS reports receiving personal fees from Merck, Ono Pharmaceutical, Bristol-Myers Squibb, Chugai Pharmaceutical, and AstraZeneca. KH reports receiving grants from MSD, AstraZeneca, Chugai Pharmaceutical, Eli Lilly, Bristol-Myers Squibb, and AbbVie; and personal fees from Pfizer, AstraZeneca, Chugai Pharmaceutical, Eli Lilly, Takeda Pharmaceutical, MSD, Bristol-Myers Squibb, Ono Pharmaceutical, Taiho Pharmaceutical, and Boehringer Ingelheim. MT reports receiving grants from Chugai Pharmaceutical, Ono Pharmaceutical, and Pfizer. KY reports personal fees from Healios, Chugai Pharmaceutical, AstraZeneca, and Bristol-Myers Squibb. SS reports receiving personal fees from MSD, Nippon Kayaku, Chugai Pharmaceutical, AstraZeneca, Ono Pharmaceutical, Bristol-Myers Squibb, Boehringer Ingelheim, Taiho Pharmaceutical, Eli Lilly, Novartis Pharma, Kyowa Kirin, Yakult Honsha, Takeda Pharmaceutical, Pfizer, Merck, Amgen, AbbVie, Otsuka Pharmaceutical, Thermo Fisher Scientific, and Towa Pharmaceutical. YT reports receiving grants from Ono Pharmaceutical, AstraZeneca, MSD, AbbVie, Bristol-Meyers Squib, Taiho Pharmaceutical, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly, Boehringer Ingelheim, Eisai, Nippon Kayaku, and Takeda Pharmaceutical; and personal fees from Ono Pharmaceutical, AstraZeneca, Bristol-Meyers Squib, Taiho Pharmaceutical, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly, Boehringer Ingelheim, Eisai, MSD, Takeda Pharmaceutical, Amgen, Novartis Pharma, Merck BioPharma, and Kyowa Kirin. YH reports receiving personal fees from AstraZeneca, Eli Lilly, Taiho Pharmaceutical, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol-Myers Squibb, Kyowa Kirin, Nippon Kayaku, Takeda Pharmaceutical, Eisai, Novartis Pharma, and Pfizer. KT reports receiving personal fees from AstraZeneca, Boehringer Ingelheim, Chugai Pharmaceutical, Daiichi Sankyo, Kyowa Kirin, MSD, and Taiho Pharmaceutical. SN reports receiving grants from AstraZeneca, Merck BioPharma, Chugai Pharmaceutical, and GlaxoSmithKline; and personal fees from AstraZeneca, Ono Pharmaceutical, Chugai Pharmaceutical, Pfizer, Eli Lilly, Takeda Pharmaceutical, Merck BioPharma, Boehringer Ingelheim, Taiho Pharmaceutical, Novartis Pharma, Daiichi Sankyo, KYORIN Pharmaceutical, and MSD. MN reports receiving personal fees from Ono Pharmaceutical, Bristol-Myers Squibb, Pfizer, Chugai Pharmaceutical, Eli Lilly, Taiho Pharmaceutical, AstraZeneca, Astellas Pharma, Boehringer Ingelheim, MSD, Novartis Pharma, Daiichi Sankyo Healthcare, Taiho Pharmaceutical, and Merck Serono. TK reports receiving grants from AbbVie, Amgen, AstraZeneca, BeiGene, Blueprint Medicines, Boehringer Ingelheim, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly, Haihe Biopharma, Merck, MSD, Novartis Pharma, Pfizer, Regeneron Pharmaceuticals, Takeda Pharmaceutical, and Turning Point Therapeutics; and personal fees from Amgen, AstraZeneca, BeiGene, Boehringer Ingelheim, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Janssen Pharmaceutical, Merck, MSD, Novartis Pharma, Ono Pharmaceutical, Pfizer, Taiho Pharmaceutical, and Takeda Pharmaceutical. TT reports receiving grants from AstraZeneca, Amgen, Boehringer Ingelheim, Merck Biopharma, Chugai Pharmaceutical, Eli Lilly, Ono Pharmaceutical, MSD, and Pfizer; and personal fees from AstraZeneca, Chugai Pharmaceutical, Eli Lilly, Ono Pharmaceutical, MSD, Pfizer, Boehringer Ingelheim, Roche Diagnostics, Takeda Pharmaceutical, and Yakult Honsha. HE reports receiving personal fees from Nippon Kayaku. MA reports receiving personal fees from Nippon Kayaku. NY reports receiving grants from Boehringer Ingelheim, Taiho Pharmaceutical, Chugai Pharmaceutical, Shionogi Pharma, Eli Lilly, Daiichi Sankyo, Tsumura, Nippon Kayaku, Asahikasei-pharma, AstraZeneca, Janssen Pharmaceutical, Sanofi, Amgen, Novartis Pharma, Astellas Pharma, MSD, Eisai, Bristol-Myers Squibb, AbbVie, and Tosoh; and personal fees from MSD, AstraZeneca, Amgen, Ono Pharmaceutical, Otsuka Pharmaceutical, Guardant Health, Tsumura, Kyowa Kirin, KYORIN Pharmaceutical, GlaxoSmithKline, Sanofi, Daiichi Sankyo, Taiho Pharmaceutical, Takeda Pharmaceutical, Chugai Pharmaceutical, Eli Lilly, Nippon Kayaku, Boehringer Ingelheim, Novartis Pharma, Pfizer, Bristol-Myers Squibb, Miyarisan Pharmaceutical, Merck, and Janssen Pharmaceutical. YO reports receiving grants from AstraZeneca, Chugai Pharmaceutical, Eli Lilly, Ono Pharmaceutical, Bristol-Myers Squibb, KYORIN Pharmaceutical, Sumitomo Pharma, Pfizer, Taiho Pharmaceutical, Novartis Pharma, Takeda Pharmaceutical, Kissei Pharmaceutical, Daiichi Sankyo, and Janssen Pharmaceutical; and personal fees from AstraZeneca, Chugai Pharmaceutical, Eli Lilly, Ono Pharmaceutical, Bristol-Myers Squibb, Boehringer Ingelheim, Bayer Yakuhin, Pfizer, MSD, Taiho Pharmaceutical, Nippon Kayaku, Kyowa Kirin, and Eisai. KN reports receiving grants from AstraZeneca, MSD, Ono Pharmaceutical, Boehringer Ingelheim, Novartis Pharma, Pfizer, Bristol-Myers Squibb, Eli Lilly, Chugai Pharmaceutical, Daiichi Sankyo, Merck Biopharma, PAREXEL International, PRA HEALTHSCIENCES, EPS, Kissei Pharmaceutical, EPS International, Taiho Pharmaceutical, PPD-SNBL, SymBio Pharmaceuticals, IQVIA Services, SYNEOS HEALTH CLINICAL, Nippon Kayaku, EP-CRSU, Mebix, Janssen Pharmaceutical, AbbVie, Bayer Yakuhin, Eisai, Mochida Pharmaceutical, Covance, Japan Clinical Research Operations, Takeda Pharmaceutical, GlaxoSmithKline, Sanofi, Sysmex, Medical Research Support, Otsuka Pharmaceutical, SRL, Pfizer R&D, and Amgen; and personal fees from Eli Lilly, KYORIN Pharmaceutical, Ono Pharmaceutical, Pfizer, Amgen, Nippon Kayaku, AstraZeneca, Chugai Pharmaceutical, MSD, Boehringer Ingelheim, Taiho Pharmaceutical, Bayer Yakuhin, CMIC ShiftZero, Life Technologies, Neo Communication, Roche Diagnostics, AbbVie, Merck Biopharma, Kyowa Kirin, Takeda Pharmaceutical, 3H Clinical Trial, Care Net, Medical Review, Medical Mobile Communications, YODOSHA, Nikkei Business Publications, Japan Clinical Research Operations, CMIC, Novartis Pharma, TAIYO Pharma, and Bristol-Myers Squibb., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Combining immunotherapy with chemotherapy can provide improved survival in advanced squamous non-small-cell lung cancer (NSCLC) patients without targetable gene alterations. 537 previously untreated patients with stage IIIB/IIIC or IV squamous NSCLC without targetable gene alterations were enrolled and randomized (2:1) to receive serplulimab 4.5 mg/kg or placebo, both in combination with nab-paclitaxel and carboplatin, intravenously in 3-week cycles. The primary endpoint of progression-free survival (PFS) was met at the first interim analysis. At the second interim analysis, PFS benefit was maintained in serplulimab-chemotherapy group (hazard ratio [HR] 0.53, 95% confidence interval [CI] 0.42-0.67). At the final analysis, serplulimab-chemotherapy significantly improved median OS compared to placebo-chemotherapy (HR 0.73, 95% CI 0.58-0.93; p = 0.010). Grade ≥3 serplulimab or placebo-related adverse events occurred in 126 (35.2%) and 58 (32.4%) patients, respectively. Our results demonstrate that adding serplulimab to chemotherapy significantly improves survival in advanced squamous NSCLC patients, with manageable safety., Competing Interests: Declaration of interests C.Z. reports receiving honoraria as a speaker from Lilly China, Sanofi, Boehringer Ingelheim, Roche, Merck Sharp & Dohme, Qilu Pharmaceutical, Jiangsu Hengrui Pharmaceuticals, Innovent Biologics, CStone Pharmaceuticals, Luye Pharma, TopAlliance Biosciences, and Amoy Diagnostics; and serving as an advisor for Innovent Biologics, Jiangsu Hengrui Pharmaceuticals, Qilu Pharmaceutical, and TopAlliance Biosciences. W.K., Q.W., H.Y., J.L., and J.Z. are employees of Shanghai Henlius Biotech, Inc., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Immune checkpoint inhibitors (ICIs) plus chemotherapy has demonstrated efficacy in resectable non-small-cell lung cancer (NSCLC), yet the optimal period of neoadjuvant immunochemotherapy is undetermined. In a phase II study (neoSCORE, NCT04459611), more neoadjuvant therapy cycles appeared to provide greater pathological remission, and patients with squamous NSCLC had a better major pathological response rate than those with nonsquamous NSCLC. Sintilimab, a monoclonal anti-PD-1 antibody, has shown encouraging antitumor activity and safety in multiple cancers, including NSCLC. Here, we describe the study design of neoSCORE II (NCT05429463), a randomized, open-label, multicenter phase III trial comparing the efficacy and safety of three cycles with four cycles of neoadjuvant sintilimab plus platinum-based chemotherapy in resectable stage IIA-IIIB squamous NSCLC. Trial registration number: NCT05429463 (ClinicalTrials.gov).

Purpose: The ORIENT-12 study demonstrated the promising results of sintilimab combined with gemcitabine and platinum (GP) therapy in squamous non-small-cell lung cancer (sqNSCLC) patients. However, the efficacy of sintilimab plus paclitaxel/nab-paclitaxel and platinum (TP) in sqNSCLC is not yet known., Methods: Real-life data were retrospectively collected from patients with untreated locally advanced or metastatic sqNSCLC who were treated with sintilimab plus TP (arm A) or sintilimab plus GP (arm B) between January 2019 and January 2021. Baseline characteristics, the efficacy of sintilimab, and adverse events were analyzed., Results: A total of 52 patients were included (arm A, n = 32 and arm B, n = 20). The overall response rate was 59.4% in arm A and 40.0% in arm B. The median progression-free survival was 13.9 months (95% confidence interval [CI], 6.9-21.0) in arm A and 8.5 months (95% CI, 6.9-10.2) in arm B (hazard ratio [HR], 0.61; 95% CI, 0.30 to 1.25; p = 0.18). The median overall survival was 21.3 months (95% CI, 13.4-29.3) in arm A and 13.3 months (95% CI, 9.1-17.5) in arm B (HR, 0.62; 95% CI, 0.28-1.36; p = 0.23). Adverse events of grade 3 or higher occurred in 37.5% of the patients in arm A and 55.0% of the patients in arm B., Conclusions: Sintilimab-TP may have similar clinical benefits compared with sintilimab-GP in patients with untreated advanced or metastatic sqNSCLC. These results require further validation by prospective randomized controlled studies., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: There has been no study so far on gemcitabine continuous maintenance therapy targeting only squamous non-small-cell lung cancer (NSCLC) patients. This study aimed to assess the efficacy and safety of cisplatin plus gemcitabine followed by maintenance gemcitabine for chemotherapy- naïve Japanese patients with advanced squamous NSCLC., Methods: The patients received 4 cycles of gemcitabine (1,000 mg/m2, days 1 and 8) and cisplatin (80 mg/m2, day 1) every 3 weeks, followed by gemcitabine alone as maintenance therapy every 3 weeks until disease progression or unacceptable toxicity. The primary end point of the study was progression-free survival (PFS) from the date of registration., Results: From May 2013 to October 2018, 26 patients were enrolled, and 25 patients received ≥1 cycle of planned treatment. Eighteen patients (69.2%) received 4 cycles of cisplatin plus gemcitabine, and 16 patients (61.5%) received ≥1 cycle of maintenance gemcitabine. The median PFS from the date of registration was 5.3 months (95% CI 2.9-7.3 months). In 16 patients who received ≥1 cycle of maintenance gemcitabine, the median PFS from the date of maintenance gemcitabine initiation was 3.8 months (95% CI 2.3-5.2 months). Their median overall survival from the date of registration was 11.9 months (95% CI 7.5-26.5 months). During the maintenance therapy, adverse events (AEs) were mostly Common Terminology Criteria for AE grade 1., Conclusions: While this trial did not meet the primary endpoint, the sufficient efficacy and feasibility of gemcitabine maintenance therapy were suggested., (© 2019 S. Karger AG, Basel.)

Background: Randomized controlled trial to evaluate synergy between taxane plus platinum chemotherapy and CADI-05, a Toll like receptor-2 agonist targeting desmocollin-3 as a first-line therapy in advanced non-small-cell lung cancer (NSCLC)., Patients and Methods: Patients with advanced NSCLC (stage IIIB or IV) were randomized to cisplatin-paclitaxel (chemotherapy group, N = 112) or cisplatin-paclitaxel plus CADI-05 (chemoimmunotherapy group, N = 109). CADI-05 was administered a week before chemotherapy and on days 8 and 15 of each cycle and every month subsequently for 12 months or disease progression. Overall survival was compared using a log-rank test. Computed tomography was carried out at baseline, end of two cycles and four cycles. Response rate was evaluated using Response Evaluation Criteria in Solid Tumors criteria by an independent radiologist., Results: As per intention-to-treat analysis, no survival benefit was observed between two groups [208 versus 196 days; hazard ratio, 0.86; 95% confidence interval (CI) 0.63-1.19; P = 0.3804]. In a subgroup analysis, improvement in median survival by 127 days was observed in squamous NSCC with chemoimmunotherapy (hazard ratio, 0.55; 95% CI 0.32-0.95; P = 0.046). In patients receiving planned four cycles of chemotherapy, there was improved median overall survival by 66 days (299 versus 233 days; hazard ratio, 0.64; 95% CI 0.41 to 0.98; P = 0.04) in the chemoimmunotherapy group compared with the chemotherapy group. This was associated with the improved survival by 17.48% at the end of 1 year, in the chemoimmunotherapy group. Systemic adverse events were identical in both the groups., Conclusion: There was no survival benefit with the addition of CADI-05 to the combination of cisplatin-paclitaxel in patients with advanced NSCLC; however, the squamous cell subset did demonstrate a survival advantage., (© The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Immunotherapy can become a crucial therapeutic option to improve the prognosis of patients with non-small-cell lung cancer (NSCLC). Here, we evaluated the impact of programmed cell death ligand-1 (PD-L1) expression in surgically resected NSCLCs., Methods: We estimated PD-L1 expression in 229 consecutive NSCLC specimens using rabbit polyclonal antibodies to human PD-L1 in a SP263 immunohistochemical assay and evaluated PD-L1 expression for potential associations with clinicopathological parameters and survival time., Results: PD-L1 expression was significantly higher in tumors from men or current smokers. Squamous cell carcinoma histology was independently associated with high PD-L1 expression according to multivariate analysis (p = 0.015). The 5-year survival rate of patients was 70%, and the difference in the 5-year survival rate according to PD-L1 expression was not statistically significant (high expression group [67%] vs. low expression group [68%]); however, the squamous cell carcinoma group exhibited significantly lower 5-year survival rates as compared to the non-squamous cell carcinoma group (53 and 71%, respectively; p = 0.026)., Conclusion: Here, we revealed high PD-L1 expression and poor prognosis observed in patients with surgically resected squamous NSCLC as compared with non-squamous NSCLC. Our results support the identification of patient subsets that most likely respond to anti-PD-1 therapy as the first step in precision medicine., (© 2017 S. Karger AG, Basel.)