Advanced Squamous Lung Cancer Research Articles

Efficacy and safety of pembrolizumab versus sintilimab treatment in patients with advanced squamous lung cancer: A real-world study in China.

e21045 Background: Both pembrolizumab and sintilimab have been approved for the first-line treatment of patients with advanced squamous lung cancer in China. The differences of the two drugs in efficacy and safety are unclear. The aim of this study was to compare the efficacy and safety in advanced squamous lung cancer patients in real world. Methods: This was a retrospective review of patients with advanced squamous carcinoma who received sintilimab or pembrolizumab in combination with chemotherapy as first-line therapy between June 2018 and April 2022 in the Chinese PLA Hospital. The aim was to compare the objective response rate (ORR), disease control rate (DCR),progression-free survival (PFS), overall survival (OS) and adverse events (AEs). Results: A total of 164 patients were enrolled, including 63 patients (38.4%) in the sintilimab-combined chemotherapy group and 101 patients (61.6%) in the pembrolizumab group. The ORR was 65.10% in the sintilimab group and 61.40% in the pembrolizumab group (P = 0.634). The DCR was 92.10% and 92.10% in two groups respectively (P = 0.991). The median PFS was 22.2 months in sintilimab group compared with 16.5 months in pembrolizumab group[ HR = 0.743; 95% CI: 0.479-1.152; P = 0.599]. Patients treated with sintilimab had a median OS of 30.7 months and a median OS did not achieve with pembrolizumab. The incidence of all treatment-related adverse events (TRAEs) was 92.1% (58/63)in the sintilimab group, and 90.1% (91/101) in the pembrolizumab group. Conclusions: Sintilimab and pembrolizumab were similar as a first-line treatment for patients with advanced squamous lung cancer in efficacy and safety. [Table: see text]

Efficacy and safety of pembrolizumab versus sintilimab treatment in patients with advanced squamous lung cancer: A real-world study in China.

Both pembrolizumab and sintilimab have been approved by the Chinese State Drug Administration (NMPA) for the first-line treatment of patients with advanced squamous lung cancer. The differences of the two drugs in efficacy and safety are unclear. To compare the real-world efficacy and safety of first-line treatments in patients with advanced squamous lung cancer. This was a retrospective review of patients with advanced squamous carcinoma who received sintilimab or pembrolizumab in combination with chemotherapy as first-line therapy between June 2018 and April 2022 in the Chinese PLA Hospital. The primary objective was to compare the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) between the two groups. Secondary objectives were to compare the disease control rate (DCR) and to analyze adverse events (AEs) between the two groups. A total of 164 patients were enrolled, including 63 patients (38.4%) in the sintilimab-combined chemotherapy group and 101 patients (61.6%) in the pembrolizumab-combined chemotherapy group. The ORR was 65.10% in the sintilimab group and 61.40% in the pembrolizumab group (P=0.634). The DCR was 92.10% and 92.10% in the sintilimab and pembrolizumab groups, respectively (P=0.991). The median PFS was 22.2 months for patients treated with sintilimab group compared with 16.5 months for patients treated with pembrolizumab group[hazard ratio (HR) = 0.743; 95% confidence interval (CI): 0.479-1.152; P = 0.599]. Patients treated with pembrolizumab did not achieve a median OS, and patients treated with sintilimab had a median OS of 30.7 months. In the sintilimab group, the incidence of all treatment-related adverse events (TRAEs) was 92.1% (58/63), and the incidence of grade 3-4 TRAEs of 42.9% (27/63). In the pembrolizumab group, the incidence of all TRAEs was 90.1% (91/101), and the incidence of grade 3-4 TRAEs was 37.6% (38/101). In the clinical treatment of Chinese patients with advanced squamous lung cancer, first-line treatment with sintilimab in combination with chemotherapy provided similar efficacy to pembrolizumab in combination with chemotherapy, and the treatment-related adverse effect profiles were comparable between the two groups, including similar rates of grade 3-4 and all adverse events.

Case Report: Abscopal Effect of Microwave Ablation in a Patient With Advanced Squamous NSCLC and Resistance to Immunotherapy

Currently, immunotherapy has been a backbone in the treatment of advanced non-small cell lung cancer (NSCLC) without driver gene mutations. However, only a small proportion of NSCLC patients respond to immune checkpoint inhibitors, and majority of patients with initial response will develop acquired resistance at 5 years, which usually manifests as oligo-progression or oligo-metastases. Evidence from multiple clinical trials indicates that local consolidative therapies could improve the prognosis of oligometastatic NSCLC patients. Herein, we reported a case of advanced squamous lung cancer which showed a durable abscopal effect from microwave ablation after acquired resistance of immunotherapy.

Phase III Non-inferiority Study Evaluating Efficacy and Safety of Low Dose Gemcitabine Compared to Standard Dose Gemcitabine With Platinum in Advanced Squamous Lung Cancer

BackgroundProlonged infusion of low dose gemcitabine (PLDG) in combination with platinum has shown promising activity in terms of improved response rate and progression free survival (PFS); especially in squamous non-small cell lung cancer (NSCLC). Hence, we conducted a phase 3 randomized non-inferiority study with the primary objective of comparing the overall survival (OS) between PLDG and standard dose of gemcitabine with platinum. MethodologyAdult subjects (age ≥ 18 years), with stages IIIB–IV, NSCLC (squamous) and ECOG performance status of ≤2 were randomized 1:1 into either carboplatin with standard dose gemcitabine (1000 mg/m2 intravenous over 30 min, days 1 and 8) (STD-G arm) or carboplatin along with low dose gemcitabine (250 mg/m2 intravenous over 6 h, days 1 and 8) (LOW-G arm) for a maximum of 6 cycles. Tumor response was assessed by RECIST criteria version 1.1 every 2 cycles till 6th cycle and thereafter at 2 monthly intervals till progression. The primary endpoint was overall survival. 308 patients were randomized, 155 in STD-G arm and 153 in LOW-G arm, respectively. ResultsThe median overall survival in STD-G arm was 6.8 months (95%CI 5.3–8.5) versus 8.4 months (95%CI 7–10.3) in the LOW-G arm (HR-0.890 (90%CI 0.725–1.092). The results with per protocol analysis were in line with these results. There was no statistical difference in progression free survival (HR-0.949; 90%CI 0.867–1.280) and adverse event rate between the 2 arms. ConclusionThis study suggests that PLDG is an alternative to the standard gemcitabine schedule in squamous NSCLC, and either of these can be selected subject to patient convenience.

Adding Immunotherapy to Chemotherapy in Advanced Squamous Lung Cancer

Adding Immunotherapy to Chemotherapy in Advanced Squamous Lung Cancer

Advanced squamous lung cancer: therapeutic options, future directions, unmet needs and results of a monocentric survey.

Lung cancer is the leading cause of cancer-related deaths in worldwide, and NSCLC represents around 85% of all lung cancers. Squamous cell lung cancer (SqCLC) is the second most common subtype and it is challenging to treat. New options have been discovered but progresses are still limited for the lack of 'druggable' mutations. Specific resources for SqCLC are limited and this condition affects treatment and outcomes. This paper describes available and emerging therapeutic options and resources that may help patients to face their disease. We have also performed a monocentric survey collecting information about smoking habit and sense of guilty and analyzed the possibility for patients to find helpful sources for their disease. The results suggest that more materials focused on SqCLC are still needed.

Afatinib treatment of a squamous lung cancer after tumor progression of nivolumab

Nivolumab prolonged disease control in a patient with advanced squamous lung cancer that was refractory to multiple treatments. The rapid eradication of cancer after the administration of nivolumab caused hemoptysis and repeated infection. Six months after immunotherapy, mediastinal lymph node metastasis developed and afatinib effectively relieved dysphonia associated with nerve paralysis.

Sequential Treatment of Advanced Squamous Lung Cancer: First-line Gemcitabine +/- platinum Followed by Second-line Taxanes +/- platinum Versus Reverse Sequence

背景与目的吉西他滨和紫杉类药物是晚期肺鳞癌常用的化疗药物，但二者在一、二线治疗中的最佳顺序尚未明确，本研究旨在分析吉西他滨单药/或联合铂类同紫杉类药物单药/或联合铂类在一、二线治疗中不同化疗顺序的疗效及毒副作用。方法回顾性分析了105例Ⅲb期-Ⅳ期肺鳞癌患者，49例为一线予吉西他滨单药/或联合铂类，进展后二线予紫杉类单药/或联合铂类治疗（G-T组）；56例为一线予紫杉类单药/或联合铂类，进展后二线予吉西他滨单药/或联合铂类治疗（T-G组）。主要研究终点为总生存（overall survival, OS），次要研究终点为无进展生存期（progression-free survival, PFS）、客观缓解率（objective response rate, ORR）、疾病控制率（disease control rate, DCR）及不良反应。结果① G-T组与T-G组中位OS分别为为18.5个月和19.0个月（P=0.520）。②G-T组与T-G组一线化疗中位PFS1分别为5.0个月和4.0个月（P=0.584）；两组二线化疗中位PFS2为2.5个月和2.7个月（P=0.432）。③G-T组与T-G组一线化疗ORR1分别为36.73%和33.92%（P=0.577），DCR1分别为79.59%和89.29%（P=0.186）；二线化疗ORR2分别为4.08%和5.36%（P=0.085），DCR2分别为51.02%和66.07%（P=0.118）。④G-T组与T-G组毒副作用相似，但G-T组更易出现Ⅲ级-Ⅳ级红细胞减低（P=0.027）和血小板减低（P=0.002）。结论一线吉西他滨单药/或联合铂类序贯二线紫杉类单药/或联合铂类与一线紫杉类单药/或联合铂类序贯二线吉西他滨单药/或联合铂类疗效相当，不良反应可耐受，两种序贯模式均对初治晚期肺鳞癌患者有效。

FGFR: Proof-of-concept study of AZD4547 in patients with FGFR1 or FGFR2 amplified tumours.

TPS2626 Background: Genetic modifications of the FGFR family of transmembrane tyrosine kinase growth factor receptors are described in a range of cancers. Amplification of FGFR2 is detected in up to 10% of oesophagogastric cancers where it is associated with poor prognosis. FGFR1 amplification has also been demonstrated in 10% of breast cancers, is more common in luminal B ER positive tumors, and is also associated with inferior survival outcomes. Finally, FGFR1 amplification has been described in up to 22% of squamous cell lung cancers. AZD4547 is a potent and selective inhibitor of FGFR-1, 2 and 3 receptor tyrosine kinases. Preclinically, AZD4547 potently inhibits growth in FGFR amplified gastric and lung cancer cell lines and induces dose dependent tumor growth inhibition and regression in FGFR amplified tumour xenograft and patient derived explant models. Methods: This is an open label, phase II non-randomised multi-centre study to assess the efficacy of AZD4547 monotherapy and resulting molecular changes in serial biopsies in pts with previously treated FGFR1 amplified advanced breast cancer, FGFR2 amplified advanced oesophagogastric cancer, or FGFR1 amplified advanced squamous lung cancer. Eligibility include centrally verified FGFR amplified tumour (ratio >2.2), PS=0-2, ability to comply with the collection of tumor biopsies (mandatory at baseline and on days 10-14), calcium and phosphate within normal limits, measurable disease (RECIST 1.1), and no history of significant eye disease. Pts may be prescreened for FGFR amplification on archival tissue while undergoing first line or adjuvant chemotherapy. Sixteen pts will be enrolled per cohort. All pts will receive AZD4547 80mg bd on a two week on, one week off schedule. The primary endpoint is correlation between change in pERK in pretreatment and day 10-14 biopsy and change in tumour diameter on week 8 CT. Secondary endpoints include ORR, DCR and PFS. Multiple exploratory translational endpoints are also planned. The study is currently open at the Royal Marsden Hospital and will open at 15 selected UK cancer centres. This study is sponsored by the Royal Marsden Hospital, funded by AstraZeneca and has been adopted to the UK National Cancer Research Network (NCRN) portfolio. Clinical trial information: 2011-003718-18.

Retrospective study of erlotinib in patients with advanced squamous lung cancer

Background: The effective targeted therapy for lung squamous cell carcinoma (SCC) is needed. The epidermal growth factor receptor (EGFR) mutation rate is low in lung SCC. The aim of this study was to evaluate the status of erlotinib treatment and EGFR mutation in lung SCC patients.Methods: We retrospectively enrolled lung cancer patients with SCC histology and history of erlotinib treatment. The primary objective was to assess overall response rate (ORR) and disease control rate (DCR) and the secondary objective was to assess progression-free survival (PFS) and overall survival (OS). EGFR mutations were assessed in parts of patients using both direct sequencing and protein nucleic acid-locked nucleic acid polymerase chain reaction (PNA-LNA PCR) clamp methods.Results: In total, 92 patients were analyzed (75 men and 17 women, median age 69 years, and 74 current or former smokers). Sixteen patients achieved partial response and 9 had stable disease. The ORR was 17.4% and the DCR was 27.2%. The PFS and OS were longer in patients with disease control than with progressive disease (PFS 7.8 versus 1.3 months and OS 20.7 versus 2.7 months, both p<0.0001). The 1-year survival rate was 21.7%. In 27 patients with adequate specimens for molecular analysis (including 4 PR and 4 SD), two (7.4%) had EGFR complex mutations. One patient experienced response to erlotinib and the other did not.Conclusions: A significant proportion of lung SCC patients would derive a clinical benefit from erlotinib treatment. The relatively higher response rate than the EGFR mutation rate in present study needs further evaluation.

Radiolocalization of squamous lung carcinoma with 131I-labeled epidermal growth factor : Cuartero-Plaza A, Martinez-Miralles E, Rosell R, Vadell-Nadal C, Farre M, Real FX. Department d'Immunologia, Carrer del Dr. Aiguader, 80, E-08003 Barcelona. Clin Canc Res 1996;2:13–20

Overexpression of epidermal growth factor receptor (EGFr) in squamous carcinomas has been demonstrated extensively. Preliminary clinical studies have shown that radiolabeled anti-EGFr monoclonal antibodies can localize to these tumors. The aims of this study were to determine the tolerance, pharmacokinetics, and radiolocalization properties of 131I-labeled EGF in patients (n = 9) with advanced squamous lung cancer. Patients' vital signs and symptoms were monitored regularly for 3 days. Daily scintigrams and biological samples for pharmacokinetic analysis were obtained for 3-4 days. 99mTc-labeled human serum albumin was administered to patients with positive tumor scans. Six patients had positive tumor scans, and five of them had received >/=1.0 mg EGF. In all of these cases, tumors were visualized the same day of the infusion, although best tumor-background contrast was obtained at 50-74 h. There were no false-positive images. Whole-body radioactivity retention rose significantly with increasing EGF doses; most labeled EGF was eliminated by urinary excretion. Tumor:normal tissue uptake ratios increased during the course of the study. All patients presented self-limited, dose-related gastrointestinal adverse effects. In conclusion, recombinant 131I-labeled EGF administered i.v. can localize to squamous lung cancer efficiently, can be administered safely to patients, and has more advantageous pharmacokinetic properties than monoclonal antibodies. Further studies are warranted to determine more accurately the potential of EGF and EGF-related peptides in the imaging and/or therapy of EGFr-overexpressing human cancers.