Second-line treatment options in Non-Small Cell Lung Cancer (NSCLC): report from an International Experts Panel Meeting of the Italian Association of Thoracic Oncology

Non-small-cell lung cancer (NSCLC) patients inevitably progress to first-line therapy and further active treatments are warranted. In the last few years, new second-line therapies, beyond chemo-agents, have become available in the clinical practice. To date, several options for the second-line treatment of non-oncogene-addicted NSCLC patients ranging from chemotherapy in combination with anti- vascular endothelial growth factor receptor to immunotherapeutics are available. In oncogene-driven tumors, the better knowledge of mechanisms of acquired resistance to earlier TKIs is leading to novel active inhibitors now available/in development. The second-line algorithm treatment of NSCLC becomes very intricate and the selection of proper patients with one of the new available therapeutic options is of paramount importance to personalize and optimize the treatment. This review will discuss the second-line treatment opportunities of both addicted and not-addicted NSCLC

Survival of bronchopulmonary cancers according to radon exposure

IntroductionResidential exposure is estimated to be responsible for nearly 10% of lung cancers in 2015 in France, making it the second leading cause, after tobacco. The Auvergne-Rhône-Alpes region, in the southwest of France, is particularly affected by this exposure as 30% of the population lives in areas with medium or high radon potential. This study aimed to investigate the impact of radon exposure on the survival of lung cancer patients.MethodsIn this single-center study, patients with a histologically confirmed diagnosis of lung cancer, and newly managed, were prospectively included between 2014 and 2020. Univariate and multivariate survival analyses were carried out using a non-proportional risk survival model to consider variations in risk over time.ResultsA total of 1,477 patients were included in the analysis. In the multivariate analysis and after adjustment for covariates, radon exposure was not statistically associated with survival of bronchopulmonary cancers (HR = 0.82 [0.54–1.23], HR = 0.92 [0.72–1.18], HR = 0.95 [0.76–1.19] at 1, 3, and 5 years, respectively, for patients residing in category 2 municipalities; HR = 0.87 [0.66–1.16], HR = 0.92 [0.76–1.10], and HR = 0.89 [0.75–1.06] at 1, 3, and 5 years, respectively, for patients residing in category 3 municipalities).DiscussionAlthough radon exposure is known to increase the risk of lung cancer, in the present study, no significant association was found between radon exposure and survival of bronchopulmonary cancers

Alectinib versus crizotinib in untreated ALK-positive non–small-cell lung cancer

Alectinib, a highly selective inhibitor of anaplastic lymphoma kinase (ALK), has shown systemic and central nervous system (CNS) efficacy in the treatment of ALK-positive non-small-cell lung cancer (NSCLC). We investigated alectinib as compared with crizotinib in patients with previously untreated, advanced ALK-positive NSCLC, including those with asymptomatic CNS disease. In a randomized, open-label, phase 3 trial, we randomly assigned 303 patients with previously untreated, advanced ALK-positive NSCLC to receive either alectinib (600 mg twice daily) or crizotinib (250 mg twice daily). The primary end point was investigator-assessed progression-free survival. Secondary end points were independent review committee-assessed progression-free survival, time to CNS progression, objective response rate, and overall survival. During a median follow-up of 17.6 months (crizotinib) and 18.6 months (alectinib), an event of disease progression or death occurred in 62 of 152 patients (41%) in the alectinib group and 102 of 151 patients (68%) in the crizotinib group. The rate of investigator-assessed progression-free survival was significantly higher with alectinib than with crizotinib (12-month event-free survival rate, 68.4% [95% confidence interval (CI), 61.0 to 75.9] with alectinib vs. 48.7% [95% CI, 40.4 to 56.9] with crizotinib; hazard ratio for disease progression or death, 0.47 [95% CI, 0.34 to 0.65]; P<0.001); the median progression-free survival with alectinib was not reached. The results for independent review committee-assessed progression-free survival were consistent with those for the primary end point. A total of 18 patients (12%) in the alectinib group had an event of CNS progression, as compared with 68 patients (45%) in the crizotinib group (cause-specific hazard ratio, 0.16; 95% CI, 0.10 to 0.28; P<0.001). A response occurred in 126 patients in the alectinib group (response rate, 82.9%; 95% CI, 76.0 to 88.5) and in 114 patients in the crizotinib group (response rate, 75.5%; 95% CI, 67.8 to 82.1) (P=0.09). Grade 3 to 5 adverse events were less frequent with alectinib (41% vs. 50% with crizotinib). As compared with crizotinib, alectinib showed superior efficacy and lower toxicity in primary treatment of ALK-positive NSCLC. (Funded by F. Hoffmann-La Roche; ALEX ClinicalTrials.gov number, NCT02075840 .)

Efficacité du Pemetrexed en 2ème ligne dans les CBNPC avancés après un intervalle libre ou un traitement de maintenance par Gemcitabine ou Erlotinib dans l'étude IFCT-GFPC 05-02

L'exposition continue des cellules tumorales à un traitement de maintenance dans les CBNPC avancé pourrait conduire à une résistance aux traitements ultérieurs. L'essai IFCT-GFPC 0502 comprenait un traitement de 2ème ligne prédéfinie par pemetrexed, permettant une évaluation post hoc de l'efficacité du P en fonction d'un traitement de maintenance par gemcitabine ou par erlotinb ou une simple observation. Méthodes: Les pts atteints d'un CBNPC de stade IIIB/IV ont été randomisés après 4 cycles de cisplatine- gemcitabine en 3 bras: observation, gemcitabine et erlotinb. Le pemetrexed a été donné comme traitement de 2ème ligne après progression de la maladie dans chaque bras. La SSP et SG ont été évalués à partir du début de traitement par pemetrexed en fonction de bras de randomisation.Résultats: sur les 464 pts randomisés, 360 pts (78%) ont reçu du pemetrexed, soit 130(84%), 114(74%) et 116 (75%)dans les bras observation, gemcitabine, erlotinb respectivement. Le taux de réponse était de 19%, 7% et 15% pour les types non-épidermoide dans les bras observation, gemcitabine, erlotinb. La durée médiane de SSP ne différaient pas entre le bras gemcitabine et observation ( 4,2 vs 3,9 mois, HR 0,81 [0,62 à 1.06]) ou entre erlotinb et observation ( 4,2 vs 3,9 mois, HR 0,83 [0,64 à 1.09]). Les données sur la SG ont montré une amélioration non significative avec la gemcitabine vs observation (HR 0,81 [de 0,61 à 1.07]) ou de erlotinb vs observation (HR 0,80 [0,61 à 1,05]), avec une médiane de 7,5, 8,3 et 9,1 mois pour les bras 0, gemcitabine, erlotinb. Les résultats étaient similaires lorsque l'analyse a été limitée au type non épidermoide. Conclusions: Le traitement de maintenance par gemcitabine ou erlotinb n'a pas altéré l'efficacité de la 2ème ligne par pemetrexed comparativement à l'utilisation après un intervalle libre.Introduction: Maintenance therapy in advanced NSCLC might lead to resistance to subsequent treatments. IFCTGFPC 0502 study showed a progression-free survival (PFS) benefit with gemcitabine or erlotinib maintenance compared to observation after cisplatin-gemcitabine chemotherapy. The trial included a pre-defined pemetrexed secondUne therapy, allowing post-hoc assessment ofits efficacy according to previous maintenance treatment or treatment-free interval. Methods: Stage IIIB/IV NSCLC patients were randomized after 4 cycles of cisplatin-gemcitabine chemotherapy to either observation or to receive maintenance therapy with gemcitabine or erlotinib. Pemetrexed was given as secondline treatment on disease progression in ail arms. PFS and overall survival (OS) were assessed from the beginning of pemetrexed therapy according to randomization arm. Results: Of the 464 randomized patients, 360 (78 %) received second-line pemetrexed (130 (84%], 114 [74%] and 116 [75%] in observation, gemcitabine and erlotinib arm, respectively). Median number ofpernetrexed cycles was 3 (1-40) in ali arms. Median PFS did not differ between gemcitabine and observation arms (4.2 vs. 3.9 months, HR [95% CI] 0.81 [0.62-1.06]) or between erlotinib and observation arms (4.2 vs. 3.9 months, HR 0.83 (0.64-1.09]). OS data showed a non-significant improvement with gemcitabine arm vs. observation arm (8.3 vs 7.5 months, HR 0.81 [0.61-1.07]) or erlotinib arm vs. observation arm (9.1 vs. 7.5 months, HR 0.80 [0.61-1.05]). Results were similar for non-squamous patients. Grade 3-4 treatment-related AEs were comparable in ali arms. Conclusions: Maintenance therapy with gemcitabine continuation or erlotinib did not impair efficacy of second-Une pemetrexed comparatively to administration after a treatment-free interval.LYON1-BU Santé (693882101) / SudocPARIS-Bib. Serv.Santé Armées (751055204) / SudocSudocFranceF

Association de radiothérapie monofractionnée et de chimiothérapie concomitante dans le traitement du carcinome bronchique à petites cellules limité au thorax (résultats d'une étude rétrospective sur 38 patients)

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Economic impact of gefitinib for refractory non-small-cell lung cancer: a Markov model-based analysis.

International audienceUNLABELLED: Few data are available on the economics of target therapy or refractory non-small-cell lung cancer (NSCLC). OBJECTIVE: To determine the mean global management costs (MC) per patient treated with gefitinib for NSCLC, and the costs of the different management phases. METHOD: A Markov approach was used to model treatment costs in a cohort of 106 patients treated with gefitinib as part of a compassionate-use program (third-line treatment) in six public-sector teaching hospitals. The economic analysis adopted the health care payer's perspective, and only direct costs were taken into account. RESULTS: The mean duration of gefitinib treatment was 4.6 +/- 5.8 months (1-29 months); median survival was 4 months, 1-year and 2-year survival rates were 12.3% and 4.7%, respectively. The mean total management cost was 39,979 euros +/- 20,279. The model showed that first- and second-line treatments accounted for respectively 29.5% and 44.1% of this cost, while gefitinib periods represented 10.7%, periods of remission 1.25%, and terminal care 14.5%. A sensitivity analysis showed that the price of gefitinib had little influence on the total cost. CONCLUSION: The cost of third-line gefitinib therapy for NSCLC appears acceptable from the healthcare payer's perspective, but this needs to be confirmed in dedicated cost-effectiveness studies

Efficacy and safety of programmed cell-death-protein-1 and its ligand inhibitors in pretreated patients with epidermal growth-factor receptor-mutated or anaplastic lymphoma kinase-translocated lung adenocarcinoma

Immune-checkpoint inhibitor (ICI) efficacy in patients with non-small cell lung cancer (NSCLC) harboring molecular alterations remains poorly elucidated. This study was undertaken to determine ICI efficacy against epidermal growth-factor receptor (EGFR)/anaplastic lymphoma kinase (ALK)/c-ros oncogene 1 (ROS1)-mutated NSCLC patients in the real-world setting. In this retrospective, multicenter study on adults with ICI-treated EGFR-mutated or ALK-or ROS1-translated NSCLCs, we analyzed clinical characteristics and outcomes: ICI-treatment duration, and progression-free survival (PFS), objective response rate, duration of response, and overall survival (OS) from immunotherapy initiation. Fifty-one NSCLC patients (mean age, 58.0 years) were included from 20 French centers: 61% were never-smokers and 59% were women. Among them, 82% had EGFR-activating mutations, 16% ALK translocations, or 2% ROS1 translocations. Before ICI therapy, patients had received a median of 3 treatment lines (including tyrosine-kinase inhibitor). The median PFS was 2.1 (95% confidence interval [CI], 1.5-3.2) months for the entire cohort, 2.2 (95% CI, 1.4-3.2) for EGFR-mutated patients, and 2.4 (95% CI, 2.1-not reached) months for ALK-translocated patients. The median OS was 14.7 (95% CI, 12.1-19.2) months for the entire population and 13.9 (95% CI, 8.8-20.0) and 19.2 (95% CI, 13.1-not reached) months for EGFR-mutated and ALK-translocated patients, respectively. Seven (13.7%) patients were treated with ICI for >9 months. Toxicities were reported in 22% (11/51), including 8% (4/51) grade ≥3. In this real-world setting, analysis of ICI PFS against EGFR-mutated or ALK-translocated NSCLC patients appeared close to that observed in pretreated unselected NSCLC patients. The more promising OS probably linked to post-ICI treatments. Large prospective studies on these patient subsets are needed. Abbreviations: ALK = anaplastic lymphoma kinase, ECOG PS = the Eastern Cooperative Oncology Group performance status, EGFR = epidermal growth-factor receptor, GFPC = French Lung Cancer Group, HR = hazard ratio, ICI = immune-checkpoint inhibitor, NSCLC = non-small-cell lung cancer, OS = overall survival, PFS = progression-free survival, ROS-1 = c-ros oncogene 1, TKIs = tyrosine-kinase inhibitors

Gemcitabine and oxaliplatin combination chemotherapy for metastatic well-differentiated neuroendocrine carcinomas: a single-center experience.

International audienceBACKGROUND:: Beyond the usual regimens based on streptozocin and doxorubicin or 5-fluorouracil, no second-line therapy of metastatic neuroendocrine tumor has gained wide acceptance. Gemcitabine and oxaliplatin are generally well tolerated and have shown activity against a wide range of malignancies. The authors assessed the efficacy of gemcitabine-oxaliplatin combination (GEMOX) in the treatment of patients with metastatic neuroendocrine tumors. METHODS:: Twenty consecutive patients with progressive disease were treated with GEMOX, in most cases after failure of other chemotherapy regimens (median = 2). Patients were followed for evidence of toxicity, response, and survival. Two patients were chemotherapy-naive at treatment initiation and were excluded from the efficacy analysis. RESULTS:: Toxicity was manageable overall; however, 6 (30%) patients had to discontinue treatment because of oxaliplatin-induced neurotoxicity (grade 2). Three (17%) of 18 patients had a partial response, median progression-free survival was 7.0 months, and median overall survival was 23.4 months. CONCLUSIONS:: Gemcitabine-oxaliplatin combination shows interesting activity and is well tolerated in pretreated patients with neuroendocrine tumors. Cancer 2009. (c) 2009 American Cancer Society