Osimertinib treatment based on plasma T790M monitoring in patients with EGFR-mutant non-small-cell lung cancer (NSCLC): EORTC Lung Cancer Group 1613 APPLE phase II randomized clinical trial.

BACKGROUND: The APPLE trial aimed to evaluate the feasibility of longitudinal plasma epidermal growth factor receptor (EGFR) T790M monitoring for the best sequencing strategy of gefitinib and osimertinib. METHODS: APPLE is a randomized, non-comparative, phase II study in patients with common EGFR-mutant, treatment-naive non-small-cell lung cancer including three arms: arm A (osimertinib upfront until RECIST progression, PD), arm B [gefitinib until emergence of circulating tumor DNA (ctDNA) EGFR T790M mutation by cobas EGFR test v2 or RECIST PD], and arm C (gefitinib until RECIST PD), and then switch to osimertinib in both arms. The primary endpoint is the progression-free survival (PFS) rate 'on osimertinib' at 18 months (PFSR-OSI-18) after randomization in arm B (H0: PFSR-OSI-18 of ≤40%). Secondary endpoints include response rate, overall survival (OS), and brain PFS. We report the results of arms B and C. RESULTS: From November 2017 to February 2020, 52 and 51 patients were randomized into arms B and C, respectively. Most patients were females (70%) and had EGFR Del19 (65%); one-third had baseline brain metastases. In arm B, 17% of patients (8/47) switched to osimertinib based on the emergence of ctDNA T790M mutation before RECIST PD, with a median time to molecular PD of 266 days. The study met its primary endpoint of PFSR-OSI-18 of 67.2% (84% confidence interval 56.4% to 75.9%) in arm B versus 53.5% (84% confidence interval 42.3% to 63.5%) in arm C, with a median PFS of 22.0 months versus 20.2 months, respectively. The median OS was not reached in arm B versus 42.8 months in arm C. Median brain PFS in arms B and C was 24.4 and 21.4 months, respectively. CONCLUSIONS: The serial monitoring of ctDNA T790M status in advanced EGFR-mutant non-small-cell lung cancer during treatment with first-generation EGFR inhibitors was feasible, and a molecular progression before RECIST PD led to an earlier switch to osimertinib in 17% of patients with satisfactory PFS and OS outcomes.

Stereotactic body radiation therapy (SBRT) as salvage treatment for early stage lung cancer with interstitial lung disease (ILD): An observational and exploratory case series of non-asian patients.

Interstitial lung disease (ILD) can coexist with early-stage lung cancer (LC) and may compromise surgery and worsen patients' outcomes. Stereotactic body radiation therapy (SBRT) is the gold standard treatment for medically inoperable early-stage lung cancer, but radiation therapy is contra-indicated for patients with ILD because of the higher risk of severe radiation-induced pneumonitis. SBRT may spare healthy lung tissue, but data are scarce in this rare population. Our exploratory case series aimed to retrospectively identify patients treated with SBRT in this setting: 19 patients were diagnosed with early-stage LC-ILD over the past 6 years and 9 received SBRT. Most of them were smokers with a median age of 71, 4 had no pathological documentation. After SBRT, 5 patients had grade I-II respiratory adverse events (AEs), but none had treatment-related grade III-IV respiratory AEs. Two patients died within 6 months of SBRT, and for both, death was related to metastatic relapse. In this case series, the radiological evolution of ILD before radiotherapy and the evolution of the radiotherapy scar on CT-Scan were also explored with different evolutionary models. This exploratory study shows available data that could be studied in a larger retrospective cohort to identify risk factors for SBRT in the LC-ILD population. The use of dosimetric data as a risk factor for SBRT should be done with cautiousness due to heterogeneous and complex dose delivery and different fractionation schedule.

First-line nivolumab plus ipilimumab versus chemotherapy in patients with unresectable malignant pleural mesothelioma: 3-year outcomes from CheckMate 743.

BACKGROUND: In the phase III CheckMate 743 study (NCT02899299), first-line nivolumab plus ipilimumab significantly improved overall survival (OS) versus chemotherapy in patients with unresectable malignant pleural mesothelioma (MPM). We report updated data with 3-year minimum follow-up. PATIENTS AND METHODS: Adults with previously untreated, histologically confirmed, unresectable MPM and Eastern Cooperative Oncology Group performance status of ≤1 were randomized 1 : 1 to nivolumab (3 mg/kg every 2 weeks) plus ipilimumab (1 mg/kg every 6 weeks) for up to 2 years, or six cycles of platinum plus pemetrexed chemotherapy. This report includes updated efficacy and safety outcomes, exploratory biomarker analyses including four-gene inflammatory expression signature score, and a post hoc efficacy analysis in patients who discontinued treatment due to treatment-related adverse events (TRAEs). RESULTS: With a median follow-up of 43.1 months, nivolumab plus ipilimumab continued to prolong OS versus chemotherapy. Median OS was 18.1 versus 14.1 months [hazard ratio (95% confidence interval), 0.73 (0.61-0.87)], and 3-year OS rates were 23% versus 15%, respectively. Three-year progression-free survival rates were 14% versus 1%, and objective response rates were 40% versus 44%. At 3 years, 28% versus 0% of responders had an ongoing response. Improved survival benefit with nivolumab plus ipilimumab versus chemotherapy was observed across subgroups, including histology. A high score of the four-gene inflammatory signature appeared to correlate with improved survival benefit with nivolumab plus ipilimumab. No new safety signals were observed with nivolumab plus ipilimumab, despite patients being off therapy for 1 year. In patients who discontinued nivolumab plus ipilimumab due to TRAEs, median OS was 25.4 months, and 34% of responders maintained their responses for ≥3 years after discontinuation. CONCLUSIONS: With 3 years' minimum follow-up, nivolumab plus ipilimumab continued to provide long-term survival benefit over chemotherapy and a manageable safety profile, supporting the regimen as standard-of-care treatment for unresectable MPM, regardless of histology.

[Immunotherapy adaptation in lung cancer during the COVID-19 pandemic]. / COVID-19 et cancer bronchique : adaptation des schémas d'immunothérapie et qualité de vie.

INTRODUCTION: COVID-19 pandemics required changes in medical practices. In thoracic oncology, pembrolizumab was doubled to 400mg every 6weeks, nivolumab to 480mg every 4weeks. The objective of our study was to assess the impact on quality of life, and on psychological state, as well as the tolerance, of this new schedule. METHODS: Thoracic oncologic patients who underwent these therapeutic changes in our center during the first COVID-19 epidemic wave were included. Their quality of life was assessed using the Quality of Life Questionnaire-30, their psychological state by the Hospital Anxiety Depression (HAD) scale. We also reported the preferred administration schedule, as well as adverse events. RESULTS: Thirty patients were included. The overall quality of life was preserved. Rates on HAD scale were low. Tolerance was acceptable. In majority, patients preferred the new procedure. They had a significantly better quality of life compared to those who preferred the old one. CONCLUSIONS: This new immunotherapy schedule in thoracic oncology is well tolerated and allows a preservation of quality of life. This therapeutic option may be favored in the context of COVID-19 pandemics.

Proposals for managing patients with thoracic malignancies during COVID-19 pandemic.

The objective of this document is to formalize a degraded mode management for patients with thoracic cancers in the context of the COVID-19 pandemic. The proposals are based on those of the French High Council for Public Health, on published data outside the context of COVID-19, and on a concerted analysis of the risk-benefit ratio for our patients by a panel of experts specialized on thoracic oncology under the aegis of the French-Language Society of Pulmonology (SPLF)/French-language oncology group. These proposals are evolving (10 April 2020) according to the situations encountered, which will enrich it, and are to be adapted to our institutional organisations and to the evolution of resources during the COVID-19 epidemic. Patients with symptoms and/or COVID-19+ are not discussed in this document and are managed within the framework of specific channels.

[Prohibition of tobacco sales to minors in France and Quebec. Comparison of legislative frameworks, their enforcement, and underage smoking]. / Interdiction de vente de tabac aux mineurs en France et au Québec. Comparaison du cadre législatif, de son application, et du tabagisme des adolescents.

BACKGROUND: Prohibition of tobacco sales to minors is a provision of the World Health Organization Framework Convention on tobacco control. This measure is effective to reduce youth tobacco use, if the legislation adopted is properly implemented and enforced. Through the examples of France and Quebec, the objective of this study is to compare legislative frameworks prohibiting tobacco sales to minors, their enforcement, and possible impact on underage smoking. METHODS: Identification of legislative instruments, reports from public health authorities, and articles addressing the focused question was performed trough Medline and Google. RESULTS: Selling tobacco products to minors under 18 years of age has been banned by the law since 1998 in Quebec and 2009 in France. In 2011, in France for individuals aged 17, compliance with the law was 15%. In 2017 in France, 94% of 17-year-old daily smokers regularly bought their cigarettes in a tobacco store. Law enforcement controls and sanctions are non-existent. In 2013 in Quebec, 23% of underage smoking students usually bought their own cigarettes in a business. The compliance rate with the prohibition law rose from 37% in 2003 to 92.6% in 2017. An approach of underage "mystery shoppers" attempting to purchase tobacco products and dedicated inspectors has been implemented, and progressive sanctions are applied in case of non-compliance. In 2013, 12.2% of Quebec high school students and, in 2017, 34.1% of French 17 year olds reported using tobacco products in the last 30 days. CONCLUSION: Only an improved law enforcement, through the training of tobacco retailer's, inspections and effective deterrent penalties for non-compliance, leads to an effective legislative measure in terms of public health.

Retrospective study of hypersensitivity reactions to chemotherapeutic agents in a thoracic oncology service.

WHAT IS KNOWN AND OBJECTIVE: With the increasing use of cancer chemotherapy agents, hypersensitivity reactions are commonly encountered. The allergic clinical symptoms are variable and unpredictable. The aim of this study was to identify the characteristics of hypersensitivity reactions and to assess the value of skin tests for platinum salts and pemetrexed in the treatment of patients with non-small cell lung cancers or malignant pleural mesothelioma. METHODS: A single-centre retrospective study was performed for 2 years. Patients treated with the drugs of interest for an advanced or metastatic non-small cell lung cancers or malignant pleural mesothelioma and who experienced hypersensitivity reactions symptoms were eligible for this study. Clinical symptoms of hypersensitivity reactions, population characteristics and administered chemotherapy regimens were identified. RESULTS: The hypersensitivity reactions frequency was rare (1.2%) and concerned 17 patients in our study. Typical clinical features of immediate hypersensitivity reactions associated with treatment were observed for nine patients (anaphylactic reactions for three cases, angioedema and hypotension associated with asthenia and heat in one case, respectively, and other cutaneous symptoms in the remaining four cases). Skin tests were positive in three patients, but only for platinum salts. The outcome after reintroduction of a negatively tested platinum salt allowed us to calculate a negative predictive value for platinum salt skin tests of 100%. For pemetrexed, skin tests were negative for all patients. WHAT IS NEW AND CONCLUSION: Skin tests could be used to diagnose hypersensitivity reactions with platinum salts or to evaluate the possibility of cross-reactions between two platinum salts. A negative skin test may predict with reasonable reliability the absence of future hypersensitivity reactions in case of reintroduction of drug infusion. Because the IgE-mediated mechanism has never been demonstrated for pemetrexed, skin tests are not valid and have no diagnostic value for this molecule. Because hypersensitivity reactions are potentially fatal adverse events, we recommend that patients who experience a hypersensitivity reactions onset should be monitored closely and clinicians must be aware of hypersensitivity reaction signs.

[Lung neuroendocrine large cell carcinoma in young women. An unusual presentation]. / Cancer neuroendocrine à grandes cellules de la femme jeune : une présentation inhabituelle.

INTRODUCTION: Lung neuroendocrine large cell carcinoma is a rare tumor with a poor prognosis. There are very few guidelines for treating this cancer but a better knowledge of its markers could improve the treatment and the prognosis. OBSERVATIONS: We report two patients who presented initially with an early stage carcinoid tumor treated with surgery. Both patients had further new neuroendocrine disease diagnosed because of intermittent carcinoid syndrome, predominantly occurring at the same time as menstruation. They were then diagnosed with metastatic lung neuroendocrine large cell carcinoma and treated with first-line cisplatin-etoposide and second-line octreotide with estrogen plus progestin. They both had a good prognosis with no disease progression to date. CONCLUSIONS: The clinical characteristics of these cases raise several questions about the pathophysiology of lung neuroendocrine large cell carcinoma and may suggest potential new treatment options. The unusual clinical presentation and good prognosis may be explained either by the second-line treatment choice or by potential molecular or hormonal biomarkers. There is a need to investigate these potential biomarkers further since they could be new therapeutic targets.

[Lung neuroendocrine large-cell carcinoma in young women - An unusual presentation]. / Cancer neuroendocrine à grandes cellules de la femme jeune : une présentation inhabituelle.

INTRODUCTION: Lung neuroendocrine large-cell carcinoma (LNELCC) is a rare tumour with a poor prognosis. There are very few guidelines for LNELCC treatment but a better knowledge of its biology could improve the treatment and prognosis of this malignancy. OBSERVATIONS: We present the cases of 2 patients who presented initially with early stage carcinoid tumours treated with surgery. Both patients had further new neuroendocrine disease diagnosed because of intermittent carcinoid syndrome, predominantly occurring at the same time as menstruation. They were then diagnosed with metastatic LNELCC. They were treated with first-line cisplatin-etoposide and second-line octreotide based on the protocol used for treatment of gastro-intestinal neuroendocrine tumours. They both had a good prognosis with no disease progression to date. CONCLUSIONS: The clinical characteristics of these cases raise several questions about the pathophysiology of LNELCC and may suggest potential new treatment options. The unusual clinical presentation and good prognosis may be explained either by the second-line treatment choice or by potential molecular or hormonal biomarkers. There is a need to investigate these potential biomarkers further since they could be new therapeutic targets.

Adrenal surgery for oligometastatic tumors improves survival in selected cases.

INTRODUCTION: Oligometastatic cancer prognosis is distinct from polymetastatic cancer prognosis and surgery can improve survival. The objective of this study was to assess the role of adrenalectomy and to look for prognostic or predictive factors for the treatment of patients with oligometastatic solid tumors and adrenal metastasis. MATERIAL AND METHODS: Patients with oligometastatic solid tumors undergoing adrenalectomy were selected. Clinical data were retrieved from electronic patients records. Progression-free survival (PFS), overall survival (OS) and clinical outcomes were assessed. RESULTS: Forty patients were analyzed. Median PFS was 7.4 months and PFS was longer for metachronous versus synchronous adrenal metastasis (10.8 versus 4.5 months; P=0.008). Median OS was 22.8 months and OS was better with laparoscopic adrenalectomy versus open adrenalectomy (24.4 versus 11.2 months; P=0.05). DISCUSSION: Adrenalectomy part of the treatment plan of oligometastatic solid tumors but patients have to be selected. Surgery might be indicated for metachronous metastasis when laparoscopic adrenalectomy is possible.

[Oncogenic drivers in daily practice improve overall survival in patients with lung adenocarcinoma]. / Bénéfice à l'évaluation moléculaire en routine pour les cancers bronchiques métastatiques.

BACKGROUND: EGFR tyrosine kinase inhibitors and crizotinib are nowadays the optimal treatment for metastatic lung cancer with activation of EGFR mutations and ALK rearrangement. In addition, several targeted agents are in development for lung cancer with other oncodrivers. In France, since 2011, six oncodrivers are routinely tested in patients with stage IV. The aim of this study was to assess whether systematic detection of oncodrivers and matched targeted therapy improve overall survival in patients with advanced lung adenocarcinoma. METHODS: This study included all consecutive patients treated in our department for advanced lung adenocarcinoma from January 2012 to December 2013. We studied the impact in survival according to the presence of the driver and the targeted therapy. RESULTS: Among the 261 patients included, oncodrivers alterations were found in 43.5% of patients: EML4-ALK fusion genes (2.1%), EGFR (10.3%), KRAS (27.7%), BRAF (2.5%), HER2 (0.8%), and PI3KCA (0.8%) mutations. Twenty-nine percent of patients (n=32) with oncodrivers received matched targeted therapy. Patient treated by targeted agent appropriate to an oncogenic driver had a median survival of 21.1 months (95% CI: 14.7-27.5). The patients (n=79) who did not receive targeted therapy had a median survival of 6.6 months (95% CI: 4.3-8.9). The patients (n=150) without identified driver had a median survival of 9.7 months (95% CI: 6.7-11.7); P<0.001. CONCLUSION: An actionable oncodriver was routinely detected in nearly half of patients with advanced lung adenocarcinoma. This systematic detection may influence treatment outcomes, notably with matched targeted therapy.

Management of malignant pleural mesothelioma: a French multicenter retrospective study (GFPC 0802 study).

BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare disease with poor prognosis in spite of significant improvement in survival, due to new chemotherapy regimens. We describe here patients' profiles and management in daily practice in France. METHODS: Observational retrospective study. Data were collected from medical files. All patients with histologically proven MPM diagnosed from January 2005 to December 2008 were included in the participating sites. RESULTS: Four hundred and six patients were included in 37 sites: mean age 68.9 ± 9.8 years, male predominance (sex ratio 3.27), latency of the disease 45.7 years, epithelioïd type 83 %. Diagnosis was made using thoracoscopy in 80.8 % of patients. Radical surgery was performed in 6.2 % of cases. Chemotherapy was administered to 74.6 % of patients. First line regimens consisted mainly of platinum + pemetrexed (91 %) or pemetrexed alone (7 %). Objective response rate was 17.2 % and another 41.6 % of patients experienced disease stabilization. Half of these patients underwent second line chemotherapy (platinium + pemetrexed 31.6 %, pemetrexed alone 24.6 %), resulting in a 6 % response rate. Third-line chemotherapy (56 patients) yielded disease control in 5.4 % of cases. CONCLUSIONS: The management of MPM in France is usually in accordance with guidelines. Response rates are somewhat lower than those described in clinical trials.

[Atypical metastatic breast localization in lung cancer]. / Localisation secondaire atypique au « sein ¼ des cancers bronchiques.

INTRODUCTION: In the context of bronchial cancers, the most frequent sites for metastases to occur are the lung, bone, brain, liver and adrenal glands. However, metastasis to other sites does additionally occur and this might be influenced by the biological characteristics of the tumour. OBSERVATION: We report the case of a 54-year-old woman with a primary bronchial adenocarcinoma with an EML4-ALK translocation. During her treatment with crizotinib, the patient developed a lesion in her right breast. The initial pathological diagnosis was of an invasive ductal adenocarcinoma of the breast. However, an additional immuno-histochemical analysis revealed it to be a metastasis from her bronchial tumour. CONCLUSION: This case is an illustration that, in the context of a lung cancer with ALK rearrangement, synchronous or secondary lesions must be interpreted with caution. Specific biological analysis - ALK immunohistochemistry or FISH - must be performed to confirm a primary or metastatic origin for these lesions.

[Ipilimumab and metastatic lung cancer: Can we change the natural history of the disease?]. / Ipilimumab et cancer bronchique métastatique : peut-on changer l'histoire naturelle de la maladie ?

INTRODUCTION: Ipilimumab (anti CTLA-4 antibody) aims to activate antitumor immunity. This treatment is being evaluated in non-small cell lung cancer. CASE REPORT: We report a case of a stage IV adenocarcinoma patient randomized in 2008 in the phase II trial CA 184-104 evaluating the combination of ipilimumab to chemotherapy with carboplatin and paclitaxel. After an initial partial response to chemotherapy, the patient achieved a complete response with ipilimumab as maintenance therapy. However, it was complicated by grade 3 gastro-intestinal toxicity leading to stop the ipilimumab. However, this complete response persists after 6 years. CONCLUSIONS: Our case illustrates the contribution of immunotherapy at least in some patients. The mechanisms of action, relationship between efficacy and toxicity and predictors of efficacy remain to be defined.

Randomized open-label non-comparative multicenter phase II trial of sequential erlotinib and docetaxel versus docetaxel alone in patients with non-small-cell lung cancer after failure of first-line chemotherapy: GFPC 10.02 study.

BACKGROUND: Concomitant administration of erlotinib with standard chemotherapy does not appear to improve survival among patients with non-small-cell lung cancer (NSCLC), but preliminary studies suggest that sequential administration might be effective. OBJECTIVE: To assess the efficacy and tolerability of second-line sequential administration of erlotinib and docetaxel in advanced NSCLC. METHODS: In an open-label phase II trial, patients with advanced NSCLC, EGFR wild-type or unknown, PS 0-2, in whom initial cisplatin-based chemotherapy had failed were randomized to sequential erlotinib 150 mg/d (day 2-16)+docetaxel (75 mg/m(2) d1) (arm ED) or docetaxel (75 mg/m(2) d1) alone (arm D) (21-day cycle). The primary endpoint was the progression-free survival rate at 15 weeks (PFS 15). Secondary endpoints included PFS, overall survival (OS), the overall response rate (ORR) and tolerability. Based on a Simon optimal two-stage design, the ED strategy was rejected if the primary endpoint was below 33/66 patients at the end of the two Simon stages. RESULTS: 147 patients were randomized (median age: 60±8 years, PS 0/1/2: 44/83/20 patients; males: 78%). The ED strategy was rejected, with only 18 of 73 patients achieving PFS15 in arm ED at the end of stage 2 and 17 of 74 patients in arm D. In arms ED and D, respectively, median PFS was 2.2 and 2.5 months and median OS was 6.5 and 8.3 months. CONCLUSION: Sequential erlotinib and docetaxel was not more effective than docetaxel alone as second-line treatment for advanced NSCLC with wild-type or unknown EGFR status.

From randomized trials to the clinic: is it time to implement individual lung-cancer screening in clinical practice? A multidisciplinary statement from French experts on behalf of the French intergroup (IFCT) and the groupe d'Oncologie de langue francaise (GOLF).

BACKGROUND: Despite advances in cancer therapy, mortality is still high except in early-stage tumors, and screening remains a challenge. The randomized National Lung Screening Trial (NLST), comparing annual low-dose computed tomography (LDCT) and chest X-rays, revealed a 20% decrease in lung-cancer-specific mortality. These results raised numerous questions. The French intergroup for thoracic oncology and the French-speaking oncology group convened an expert group to provide a coherent outlook on screening modalities in France. METHODS: A literature review was carried out and transmitted to the expert group, which was divided into three workshops to tackle specific questions, with responses presented in a plenary session. A writing committee drafted this article. RESULTS: The multidisciplinary group favored individual screening in France, when carried out as outlined in this article and after informing subjects of the benefits and risks. The target population involves subjects aged 55-74 years, who are smokers or have a 30 pack-year smoking history. Subjects should be informed about the benefits of quitting. Screening should involve LDCT scanning with specific modalities. Criteria for CT positivity and management algorithms for positive examinations are given. CONCLUSIONS: Individual screening requires rigorous assessment and precise research in order to potentially develop a lung-cancer screening policy.

A multicenter phase II randomized trial of gemcitabine followed by erlotinib at progression, versus the reverse sequence, in vulnerable elderly patients with advanced non small-cell lung cancer selected with a comprehensive geriatric assessment (the GFPC 0505 study).

BACKGROUND: The aim of this randomized phase II trial was to evaluate the feasibility and activity of weekly gemcitabine (G) followed by erlotinib at disease progression (arm A) versus erlotinib followed by G at progression (arm B) in vulnerable elderly patients with advanced non small-cell lung cancer (NSCLC), selected on the basis of a comprehensive geriatric assessment (CGA). METHODS: Vulnerable elderly chemotherapy-naive patients with stage IIIB/IV NSCLC were selected after a CGA (socioeconomic, cognitive and emotional status, depression, nutritional status, ADL and IADL assessments). The primary endpoint was the time to second progression (TTP2). Overall survival (OS), time to first progression (TTP1) and safety were secondary endpoints. RESULTS: Between May 2006 and January 2010, 21 centers enrolled 100 patients, of whom 94 were eligible. TTP2 was 4.3 and 3.5 months in arm A and arm B, respectively; TTP1 was 2.5 and 2.2 months; and the median OS time was 4.4 and 3.9 months. The respective one-year survival rates were 27.3% and 20%. There was no major unexpected toxicity. CONCLUSION: In vulnerable elderly patients with NSCLC not selected for EGFR expression, both strategies were feasible but had modest efficacy. Further studies are needed to identify elderly patients who should receive palliative care only.

[Anti-angiogenic factors in thoracic oncology: successes, failures and prospects]. / Traitements antiangiogéniques en oncologie thoracique: succès, échecs et perspectives.

Many growth factors involved in tumor angiogenesis are potential targets in thoracic oncology. This work is a review of the literature on the effectiveness of anti-angiogenic treatments in non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC) and malignant pleural mesothelioma (MM). Thirty-four articles and 15 abstracts were identified. Currently, bevacizumab is the only drug that has demonstrated an impact on overall survival in first line treatment for stage IV non-squamous NSCLC, but VEGFR-TKI such as cediranib, aflibercept, vandetanib, pazopanib have shown encouraging results in phase II or III clinical trials. In extensive-disease SCLC and inoperable MM, bevacizumab is the most studied molecule, but again, clinical trials are still ongoing. Current data on potential predictors for efficacy are disappointing, but some biomarkers or radiological techniques might be useful for guiding the use of anti-angiogenic therapies in the future. In conclusion, bevacizumab is the most studied anti-angiogenic agent in thoracic oncology. It is the only approved drug with an indication in first-line and maintenance treatment for stage IV non-squamous NSCLC. The indications for the use of VEGFR-TKI in clinical practice remain to be defined.