Explore the vast range of titles available.

The prognosis of advanced non-small-cell lung cancer (NSCLC) has been improved by development of immune checkpoint inhibitors (ICIs) such as nivolumab for second-line treatment. As phase III trials include only selected patients, we here investigated the clinical factors associated with efficacy and safety of nivolumab in 'real life' patients with advanced NSCLC. Clinical and histological characteristics, therapies and survival data of all consecutive patients with advanced NSCLC included prospectively and treated by nivolumab in two French academic hospitals between February 2015 and December 2016 were examined. Sixty-seven patients were included, mostly male (69%), current or former smokers (87%) with PS <2 (73%). Median age was 68.5 years and 42% were aged ≥70 years. According to uni- and multi-variate analyses, only PS 2 (OR = 0.17, 95% CI 0.03-0.99, p = 0.049) and number of previous treatment lines (OR = 0.33, 95% CI 0.13-0.85, p = 0.022) were significantly negatively associated with tumor control. Worse progression-free survival (PFS) was significantly associated with PS 2 (HR = 5.17, 95% CI 1.99-13.43, p = 0.001) and use of steroids (HR = 3.27, 95% CI 1.39-7.69, p = 0.006). Worse overall survival was associated with symptomatic brain metastasis (HR = 3.15, 95% CI 1.23-8.85, p = 0.029). Treatment-related adverse events occurred in 47 patients (70%), symptomatic brain metastasis being significantly associated with Grade ≥3 toxicity (OR = 8.13, 95% CI 1.21-55.56, p = 0.031). Age and nutritional status were not associated with response, PFS, OS or toxicity. Our results suggest that nivolumab is not beneficial or safe for patients with PS 2 and symptomatic brain metastases.

The current first-line standard treatment for advanced small cell lung cancer (SCLC) is a combination of chemotherapy and immunotherapy. However, few efficacy data are available in a real-life settings, including frail patients. The aim of this study is to describe the real-life efficacy of chemoimmunotherapy in an unselected SCLC population. We conducted a retrospective multicenter study, which compared two cohorts of patients with treatment-naive metastatic SCLC treated in six academic centers in the Greater Paris area. Cohort 1 included patients treated with chemotherapy between January 2017 and December 2018, and cohort 2 included patients treated with chemoimmunotherapy between January 2019 and December 2020. A total of 153 consecutive patients were included (cohort 1: n = 96; cohort 2: n = 57). Clinical characteristics were similar between the two cohorts. Overall survival (OS) was statistically higher in cohort 2 (median survival 15.47 months) than in cohort 1 (median survival 9.5 months) (p = 0.0001). OS for patients with a performance status ≥2 and for patients ≥70 years old was not statistically different between the two cohorts. Chemoimmunotherapy efficacy was better compared to chemotherapy alone in case of brain or liver metastases. In conclusion, the combination of chemoimmunotherapy in metastatic SCLC appears to provide a real-life OS benefit. Dedicated clinical trials are needed to test this strategy in patients with impaired performance status or advanced age.

Herein, we report a case of a 73‐year‐old female patient diagnosed with cT4N0M1a lung adenocarcinoma with KRAS G12C mutation, PDL1 < 1% and treated in fourth‐line setting with gemcitabine after progression under nivolumab. After one infusion of gemcitabine, the patient presented with an acute worsening of general condition (performance status 4) with extensive skin lesions and fever, leading to hospitalization and diagnosis of acute generalized exanthematous pustulosis. Initial blood work revealed multiple organ failures with an important inflammatory syndrome. Patient state improved after intravenous hydration and local and systemic corticosteroids. The decision was made to stop systemic cancer treatment. Two months follow‐up showed a remarkable response on all cancer localizations. Although immunotherapy is transforming cancer care, predicting response to immunotherapy remains challenging and resistant mechanisms remain mostly unknown. This case underlines that important immune‐stimulation can lead to tumor response in a patient previously refractory to all antitumor treatments. Acute generalized exanthematous pustulosis (AGEP) causes T cell migration to the dermis and epidermis followed by the chemotaxis of neutrophils. We hypothesize that the major immune reaction caused by AGEP led to an effective antitumor immune response in our patient still exposed to nivolumab due to its prolonged half‐life. Immunotherapy is transforming lung cancer treatment. Predicting its efficacy remains challenging with unreliable predictive markers and might be influenced by acute immune reactions. We report a case of a patient treated for metastatic lung adenocarcinoma. She had recently progressed under third‐line nivolumab. After one cycle of fourth‐line gemcitabine, she presented experienced an acute generalized exanthematous pustulosis causing major immune stimulation and major durable tumor response.

Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for patients with non-small cell lung cancer (NSCLC). Although some patients can experience important response rates and improved survival, many others do not benefit from ICIs developing hyper-progressive disease or immune-related adverse events. This underlines the need to select biomarkers for ICIs use in order to better select patients. There is currently no universally validated robust biomarker for daily use of ICIs. Programmed death-ligand 1 (PD-L1) or tumor mutational burden (TMB) are sometimes used but still have several limitations. Plasma biomarkers are a promising approach in ICI treatment. This review will describe the development of novel plasma biomarkers such as soluble proteins, circulating tumor DNA (ctDNA), blood TMB, and blood microbiome in NSCLC patients treated with ICIs and their potential use in predicting response and toxicity.

Tyrosine kinase inhibitors (TKIs) are used as targeted cancer therapies in adults and have an off-label pediatric application for the treatment of Langerhans cell histiocytosis. A multitarget LC-MS/MS method was developed and validated for the determination of alectinib, alectinib-M4, binimetinib, cobimetinib, crizotinib, dabrafenib, encorafenib, imatinib, lorlatinib, osimertinib, AZ5104, and trametinib. A total of 150 µL of internal standard methanolic solution was added to 50 µL of plasma sample to precipitate proteins. After centrifugation, 10 µL of the supernatant was injected into the chromatographic system. The chromatographic separation was conducted on a Kinetex C18 Polar column with a gradient of 2 mM ammonium formate in 0.1% formic acid and acetonitrile over 5 min. Limits of detection and quantification, linearity, accuracy, precision, selectivity, carryover, matrix effect, recovery, and stability were evaluated and satisfied EMA guidelines on bioanalytical methods. This method has been successfully applied to the therapeutic drug monitoring (TDM) of adults with melanoma and lung cancer, as well as children with histiocytosis, to improve the pharmacokinetic data for these drugs, with the aim of enhancing the therapeutic management and follow-up of patients. Blood concentrations of trametinib and binimetinib were different in the two groups, highlighting the age-related inter-individual variability of these molecules and the need for TDM.

Introduction: Compared with docetaxel, the phase-III trial, ULTIMATE, showed a significant improvement of progression-free survival (PFS) with paclitaxel–bevacizumab combination (PB) as second- or third-line treatment in advanced non-small cell lung cancer (NSCLC). With the increase of immunotherapy treatment in first-line settings, the optimal treatment after first-line failure must be redefined. Methods: This multicentric retrospective study identified all advanced NSCLC patients treated with PB as second-line therapy and beyond. The main efficacy outcomes assessed were objective response rate (ORR), disease control rate (DCR), PFS, and overall survival (OS). The adverse events were reported according to Common Terminology Criteria for Adverse Events (CTCAE). Results: From January 2010 to February 2020, 314 patients in 16 centers received the PB combination. Most patients were male (55%), with a median age of 60 years (19–82), 95% had adenocarcinoma, 27% had a performance status ⩾2, 45% had brain metastases at the time of inclusion. They mostly received the PB combination either in second (20%) or in third-line (39%), and 28% were treated just after ICI failure. ORR and DCR were 40% and 77%, respectively; median PFS and OS were 5.7 [interquartile range (IQR): 3.2–9.6] and 10.8 [IQR: 5.3–19.6] months, respectively. All grade adverse events concerned 82% of patients, including 53% asthenia and 39% neurotoxicity, and 25% of patients continued monotherapy (mostly with bevacizumab) alone due to toxicity. Median PFS for patients treated after ICI failure (ICI+) was significantly superior compared with those not previously treated with ICI (ICI−): 7.0 [IQR: 4.2–11.0] versus 5.2 [IQR: 2.9–8.8] months, p = 0.01, without statistically significant difference for OS between these two groups. In multivariate analysis, factors associated with superior PFS were previous ICI treatment and performance status of 0–1. Only a performance status of 0–1 was associated with superior OS. Conclusion: PB combination as second-line treatment or beyond for advanced non-squamous NSCLC had acceptable toxicity and a clinically relevant efficacy and is an option as salvage treatment for these patients, more particularly after ICI progression.

Hedgehog signaling pathway is physiologically activated during embryogenesis, especially in lung development. It is also reactivated in many solid tumors. In lung cancer, Hedgehog pathway is closely associated with cancer stem cells (CSCs). Recent works have shown that CSCs produced a full-length Sonic Hedgehog (Shh) protein, with paracrine activity and induction of tumor development. Hedgehog pathway is also involved in tumor drug resistance in lung cancer, as cytotoxic chemotherapy, radiotherapy, and targeted therapies. This review proposes to describe the activation mechanisms of Hedgehog pathway in lung cancer, the clinical implications for overcoming drug resistance, and the perspectives for further research.

Background Lepidic predominant adenocarcinoma is characterized by frequent refractory hypoxemia due to intrapulmonary shunting. Severe hypoxemia can induce perioperative complications in case of thoracic surgery. Case presentation We report a case of a 67 year-old woman with localized lepidic adenocarcinoma in the right lower lobe with severe hypoxemia. A selective arterial lung embolization allowed an instantaneous correction of the hypoxemia, and a curative lobectomy was safely performed 1 week after without any complication. The staging was pT3N0M0, and the patient received adjuvant chemotherapy. Conclusions This is the first case-report of successful endovascular embolization before curative surgery for a lepidic predominant lung adenocarcinoma.

Around 4% of advanced non-small-cell lung cancers (NSCLCs) have an rearrangement at the time of diagnosis. This molecular feature is more frequent in young patients, with no/light smoking habit and with adenocarcinoma pathological subtype. Crizotinib is a tyrosine kinase inhibitor, targeting ALK, ROS1, RON, and MET. The preclinical efficacy results led to a fast-track clinical development. The US Food and Drug Administration (FDA) approval was achieved after the Phase I clinical trial in 2011 in ALK-rearranged advanced NSCLC progressing after a first-line treatment. In 2013, the randomized Phase III trial PROFILE-1007 confirmed the efficacy of crizotinib in ALK-rearranged NSCLC, compared to cytotoxic chemotherapy, in second-line setting or more. In 2014, the PROFILE-1014 trial showed the superiority of crizotinib in the first-line setting compared to the pemetrexed platinum doublet chemotherapy. The response rate was 74%, and the progression-free survival was 10.9 months with crizotinib. Based on these results, crizotinib received approval from the FDA and European Medicines Agency for first-line treatment of ALK-rearranged NSCLC. The various molecular mechanisms at the time of the progression (ALK mutations or amplification, ALK-independent mechanisms) encourage performing re-biopsy at the time of progression under crizotinib. The best treatment strategy at the progression (crizotinib continuation beyond progression, switch to second-generation tyrosine kinase inhibitors, or cytotoxic chemotherapy) depends on the phenotype of the progression, the molecular status, and the physical condition of the patient.

Introduction There is a need for biomarkers to predict response and survival to immune checkpoint inhibitors (ICIs) in patients with advanced non-small cell lung cancer (NSCLC). Soluble PD-L1 (sPD-L1) has shown biomarker potential. The objective of this study was to evaluate sPD-L1 in patients with advanced NSCLC treated with first-line ICIs. Methods We constructed three prospective cohorts of patients with advanced NSCLC treated with first-line chemotherapy (CT), (Cohort #1), ICIs, or CT-ICIs (Cohort #2 and #3). Plasma was collected at baseline and at first tumour evaluation. sPD-L1 levels were measured by ELISA and compared to response and survival metrics. Results Patients were mostly male smokers with adenocarcinomas. Baseline sPD-L1 was lower in responders versus (vs) non-responders in Cohort #2 ( p  = 0.0233). Patients with low baseline sPD-L1 had longer OS in Cohorts #2 and #3: median OS 18.0 months vs 4.0 months, ( p  = 0.0277) and not reached (NR) vs 13.0 months ( p  = 0.0360). First tumour evaluation sPD-L1 was lower in responders in Cohorts #1 ( p  = 0.0138) and #2 ( p  = 0.0009). Patients with low sPD-L1 at first tumour evaluation had longer OS in Cohort #2: 45.0 months vs 12.5 ( p  = 0.0041). Patients with stable/decreasing sPD-L1 had longer OS throughout the Cohorts: median OS of 15.5 vs 6.0 months, 45.0 vs 14.0 months and not reached (NR) vs 17.0 months in Cohorts #1, #2 and #3. In vitro studies confirmed that cancer and immune cells secreted sPD-L1 and that NSLC patient plasma has the capacity to inhibit lymphocyte proliferation. Conclusion sPD-L1 has prominent biomarker potential in advanced NSCLC treated with first-line ICIs.