In the phase III ULTIMATE trial,19 166 patients with advanced NSCLCs progressing after first- or second-line therapy were randomized to receive weekly the paclitaxelCBVZ combination compared to docetaxel; progression-free survival (PFS) was significantly longer for the former group but overall survival (OS) was comparable for the two groups. New agents with antiVEGF activity have been designed for SQ-NSCLCs.20 A phase III trial that included 1253 randomized patients (all NSCLC histology, 25% SQ-NSCLCs) compared docetaxel (75 mg/m2) in combination with ramucirumab (10 mg/kg) or placebo.21 Ramucirumab adjunction to docetaxel was associated with significantly prolonged PFS and OS. contraindications that those with scores of 0. Conclusion Almost half of the SQ-NSCLC patients included in this study would have been eligible to receive an antiVEGF agent. The development of these molecules for these indications should be encouraged. strong class=”kwd-title” Keywords: lung cancer, squamous non-small cell, antiangiogenic treatments Introduction Lung cancer is the first cause of cancer deaths of men and women in the United States,1 with a 5-12 months survival rate of ~16%.2,3 Lung cancers are separated into two major categories based on histology, clinical management and prognosis: non-smallCcell lung cancer (NSCLC) and small-cell lung cancer (SCLC).3 NSCLCs represent more than 85% of these tumors.4 Its two major histologies are non-squamous and squamous (SQ) carcinomas, with the latter representing 30% of NSCLCs.4 NSCLC outcomes changed remarkably during the early 2000s, particularly for advanced lung adenocarcinomas.4 Those changes reflect the development of new brokers devoted to specific oncological drivers: inhibitors of epidermal growth factor-receptor (EGFR), anaplastic lymphoma kinase (ALK) and vascular endothelial growth factor (VEGF), and finally immunotherapy.5,6 However, median survival time was not prolonged for SQ-NSCLCs.7 The difference between the two subtypes may be due to a modest effect against SQ-NSCLCs of the agents used to treat adenocarcinomas.8,9 Therefore, immune-checkpoint inhibitors (ICIs) for SQ-NSCLCs, developed after those for non-squamous NSCLCs, could modify their prognoses.10 Because angiogenesis is a pejorative factor for several tumors, inhibiting proangiogenic factors represents a potential avenue for therapeutic development.9 While the role of VEGF in angiogenesis is well established,9,11,12 studies on SQ-NSCLCs have been limited9,11C13 by concerns about life-threatening pulmonary hemorrhage14,15 and guidelines excluded these patients from the indication.16 Bevacizumab (BVZ) was the first agent targeting VEGF to prolong survival when combined with chemotherapy for selected NSCLC patients.6,14 Despite BVZs demonstrated efficacy in phase II and III trials on NSCLC patients,5,9 adverse events like significant bleeding, including major hemoptysis, delayed its development for SQ-NSCLC patients.15,16 Tolerability of BVZ in combination with chemotherapy was established in a phase I trial on all NSCLC subtypes.17 In an early phase II trial of BVZ for NSCLC patients,18 among six patients experiencing life-threatening pulmonary hemorrhages, four had SQ-NSCLCs; four of the six patients died. Pertinently, all six patients had centrally located tumors close to major blood vessels and five had cavitation or necrosis. Results of observational studies confirmed BVZ safety11,12 and excluded certain initial contraindications, like brain metastases. Multiple trials have evaluated BVZ as second-line therapy. In the phase III ULTIMATE trial,19 166 patients with advanced NSCLCs progressing after first- or second-line therapy were randomized to receive weekly Biricodar dicitrate (VX-710 dicitrate) the paclitaxelCBVZ combination compared to docetaxel; progression-free survival (PFS) was significantly longer for the former group but overall survival (OS) was comparable for the two groups. Biricodar dicitrate (VX-710 dicitrate) New brokers with antiVEGF activity have been designed for SQ-NSCLCs.20 A phase III trial that included 1253 randomized patients (all NSCLC histology, 25% SQ-NSCLCs) compared docetaxel (75 mg/m2) in combination with ramucirumab (10 mg/kg) or placebo.21 Ramucirumab adjunction to docetaxel was associated with significantly prolonged PFS and OS. That OS benefit was also retained for the SQ-NSCLC subgroup (respective median OS, 9.5 vs 8.2 months).22 Those results led to the US Food and Drug Administration and European Medicines Agency approvals of ramucirumab for both NSCLC histologies. Nintedanib, a multitarget antiangiogenic agent, was evaluated in combination with docetaxel in a large phase III randomized trial,9,23 comparing docetaxel to placebo for all those NSCLC histological subtypes. Significantly improved OS rates were obtained for patients randomized to receive docetaxel and nintedanib vs placebo: those whose adenocarcinomas progressed within medians of 10.9 vs 7.9 months, respectively, and for the entire Biricodar dicitrate (VX-710 dicitrate) adenocarcinoma subset (12.6 vs 10.3 months). However, the entire study population did not benefit from OS prolongation. The European Medicines Agencybut neither the Biricodar dicitrate (VX-710 dicitrate) US Food and Drug Administration nor Health Canadaapproved Cd200 nintedanib to treat non-squamous NSCLCs. However, few real-life data from SQ-NSCLC patients are available. This study was undertaken to assess prospectively the clinical and radiological characteristics of advanced SQ-NSCLC patients about to receive second-line therapy to determine the percentage of them who would have been eligible to receive antiVEGF therapy. Methods This observational, multicenter, prospective study.