BRAF mutations occurring in 1%–5% of patients with non-small-cell lung cancer (NSCLC) are therapeutic targets for these cancers but the impact of the exact mutation on clinical activity is unclear. ...The French National Cancer Institute (INCA) launched the AcSé vemurafenib trial to assess the efficacy and safety of vemurafenib in cancers with various BRAF mutations. We herein report the results of the NSCLC cohort.
Tumour samples were screened for BRAF mutations in INCA-certified molecular genetic centres. Patients with BRAF-mutated tumours progressing after ≥1 line of treatment were proposed vemurafenib 960 mg twice daily. Between October 2014 and July 2018, 118 patients were enrolled in the NSCLC cohort. The primary outcome was the objective response rate (ORR) assessed every 8 weeks (RECIST v1.1). A sequential Bayesian approach was planned with an inefficacy bound of 10% for ORR. If no early stopping occurred, the treatment was of interest if the estimated ORR was ≥30% with a 90% probability. Secondary outcomes were tolerance, response duration, progression-free survival (PFS), and overall survival (OS).
Of the 118 patients enrolled, 101 presented with a BRAFV600 mutation and 17 with BRAFnonV600 mutations; the median follow-up was 23.9 months. In the BRAFnonV600 cohort, no objective response was observed and this cohort was stopped. In the BRAFV600 cohort, 43/96 patients had objective responses. The mean Bayesian estimated success rate was 44.9% 95% confidence intervals (CI) 35.2%–54.8%. The ORR had a 99.9% probability of being ≥30%. Median response duration was 6.4 months, median PFS was 5.2 months (95% CI 3.8–6.8), and OS was 10 months (95% CI 6.8–15.7). The vemurafenib safety profile was consistent with previous publications.
Routine biomarker screening of NSCLC should include BRAFV600 mutations. Vemurafenib monotherapy is effective for treating patients with BRAFV600-mutated NSCLC but not those with BRAFnonV600 mutations.
ClinicalTrials.gov identifier: NCT02304809.
•Vemurafenib monotherapy is effective for BRAFV600-mutated NSCLC.•Vemurafenib monotherapy is not effective for BRAFnonV600-mutated NSCLC.•Vemurafenib is a treatment option for BRAFV600-mutated NSCLC patients when the dabrafenib/trametinib combination is not feasible or not reimbursed.•Routine biomarker screening of NSCLC should include BRAFV600 mutations.
Immunotherapy using inhibitors targeting immune checkpoint programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) is currently the standard of care in patients with advanced ...non-small-cell lung cancer (NSCLC).
We carried out a nationwide cohort retrospective study of consecutive patients with advanced, refractory NSCLC who received nivolumab as second to later lines of treatment as part of the expanded access program. Key objectives were to assess the efficacy and safety of nivolumab and the efficacy of first post-nivolumab treatment.
Nine hundred and two patients were enrolled: 317 (35%) with squamous cell carcinoma and 585 (65%) with non-squamous cell carcinoma. Median age was 64 years; there were 630 (70%) men, 795 (88%) smokers, 723 (81%) patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0/1, 197 (22%) patients with brain metastases, and 212 (27%) with liver metastases. Best response was partial response for 16.2% and stable disease (SD) for 30.5%. Progression-free survival and overall survival (OS) rates at 2, 3, and 5 years were 8% and 25%, 6% and 16%, and 4% and 10%, respectively. At multivariate analysis, ECOG PS ≥2 hazard ratio (HR) = 2.13, 95% confidence interval (95% CI) 1.78-2.55, P < 0.001, squamous histology (HR = 1.17, 95% CI 1.01-1.36, P = 0.04), and presence of central nervous system metastases (HR = 1.29, 95% CI 1.08-1.54, P = 0.005) were significantly associated with lower OS. Four hundred and ninety-two patients received at least one treatment after discontinuation of nivolumab, consisting of systemic therapies in 450 (91%). Radiation therapy was delivered to 118 (24%) patients.
The CLINIVO cohort represents the largest real-world evidence cohort with the use of immune checkpoint inhibitor in advanced, metastatic NSCLC after failure of first-line chemotherapy, with long-term follow-up and analysis of subsequent therapies. Our data confirm the efficacy of nivolumab in a cohort larger than that reported in landmark clinical trials and identify prognostic factors, which reinforces the need for accurate selection of patients for treatment with immune checkpoint inhibitors. Our data indicate that oligoprogression is frequent after nivolumab exposure and provide a unique insight into the long-term survival.
•CLINIVO is the largest real-world evidence cohort with second-line nivolumab.•Progression-free survival and OS rates at 5 years were 4% and 10%, respectively.•Oligoprogression after nivolumab is frequent, with eligibility to radiotherapy.
ROS1-rearranged (ROS1+) non-small-cell lung cancer (NSCLC) is a rare lung cancer with limited treatment options. Phase I-II studies with ROS1-tyrosine kinase inhibitors (TKIs) included small numbers ...of patients and real-world data are lacking. We investigate the efficacy and safety of lorlatinib, a third-generation TKI targeting ALK and ROS1, in patients with ROS1+ NSCLC treated through an expanded access program.
Consecutive patients with advanced ROS1+ NSCLC treated with lorlatinib between October 2015 and June 2019 were included. Data were collected from medical records. The primary endpoint was progression-free survival.
Out of the 80 patients included, 47(59%) were female, 49(62%) never smokers (less than 100 cigarettes over the lifetime), and 68(85%) had stage IV NSCLC at diagnosis. Most frequent histology was adenocarcinoma (95%) and median age was 58.2 years. At the time of lorlatinib initiation, 51(64%) patients had brain metastases and 55(81%) were PS 0-1. Lorlatinib was administered as second/third/fourth/fifth+ line in 29%/28%/18%/26% of patients. All patients previously received at least one ROS1 TKI, and 55(69%) previously received chemotherapy. Median follow-up from lorlatinib initiation was 22.2 months. Median progression-free survival and overall survival from lorlatinib initiation were 7.1 months 95% confidence interval (CI) 5.0-9.9 months and 19.6 months (95% CI 12.3-27.5 months). Median duration of treatment with lorlatinib was 7.4 months (95% CI 6.5-13.1 months). Overall response and disease control rates were 45% and 82%, respectively. The central nervous system response rate was 72%. Treatment was stopped due to toxicity in 10 patients (13%). The safety profile was consistent with previously published data.
Lorlatinib is a major treatment option for advanced refractory ROS1+ NSCLC in treatment strategy.
•Data are lacking on lorlatinib efficacy in advanced refractory ROS1+ NSCLC.•Lorlatinib median progression-free survival and objective response rate were 7.1 months and 45%, respectively.•Lorlatinib represents a major treatment option for patients with a ROS1+ NSCLC.
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.
Sleep apnea (SA) was reported as possibly exacerbating symptoms of COVID-19, a disease induced by SARS-CoV-2 virus. The same comorbidities are common with both pathologies. This study aimed to ...estimate the prevalence, characteristics of SA and variation in AHI three months after severe COVID-19 requiring intensive care unit (ICU) admission.
A prospective cohort of patients admitted to ICU for severe COVID-19 underwent an overnight home polygraphy 3 months after onset of symptoms, as part of a comprehensive follow-up program (pulmonary function tests, 6-minute walk tests and chest CT-scan). Patients with an apnea hypopnea index (AHI) ≥5 were considered as having SA. We performed a comparative descriptive analysis of 2 subgroups according to the existence, severity of SA and indication for effective SA treatment: patients with absent or mild SA (AHI <15) vs patients with moderate to severe SA (AHI ≥15).
Among 68 patients included, 62 (91%) had known comorbidities (34 hypertension, 21 obesity, 20 dyslipidemia, 16 type 2 diabetes). It has been observed a preexisting SA for 13 patients (19.1%). At 3 months, 62 patients (91%) had SA with 85.5% of obstructive events. Twenty-four patients had no or a mild SA (AHI <15) and 44 had moderate to severe SA (AHI ≥15). Ischemic heart disease exclusively affected the moderate to severe SA group. Except for thoracic CT-scan which revealed less honeycomb lesions, COVID-19 symptoms were more severe in the group with moderate to severe SA, requiring a longer curarization, more prone position sessions and more frequent tracheotomy.
SA involved 91% of patients in our population at 3 months of severe COVID-19 and was mainly obstructive type. Although SA might be a risk factor as well as consequences of ICU care in severe COVID-19 infection, our results underline the importance of sleep explorations after an ICU stay for this disease.
Abstract Purpose In the context of CPOE of standardized antineoplastic drugs, the objectives of the present study were to determine the incidence of prescribing medication errors (PME) and to analyse ...PME related to antineoplastic treatment in university teaching hospitals. Methods : All consecutive prescribing medication orders over 1 year were analysed prospectively. Potential clinical impact was quoted according to the Hatoum scale and risk factors identified with a logistic-regression model. Results : A total of 14,854 prescriptions were analysed. The PME incidence was estimated at 1.5% 1.3–1.7, i.e. 15 errors per 1000 prescribing medication orders, with a significant or very significant potential clinical impact in 62.9% of cases. Potentially death-threatening events were avoided in 3.7% of cases. Overall, PME incidence related to significant, very significant or vital potential clinical impact was estimated to be 1.0% 0.8–1.2, i.e. 10 errors per 1000 prescribing medication orders. The most common type of error was related to antineoplastic drug dosage (61.0%): inadequate adaptation (43.1%), not taking alarms into account (16.1%), incorrect weight (0.9%), incorrect unit (0.9%). More than 20% of PME are medication errors directly linked to the prescribing medication order (choice of antineoplastic treatment, double-prescribing medication order, forgotten or not validated by a resident or senior physician). Occasional users of the CPOE system and resident physicians were identified as main PME risk factors. Conclusion : An epidemiologic survey of PME in the context of the use of a partial CPOE has allowed to determine the incidence and epidemiology of PME as well as the potential clinical impact they represent. Two risk factors have emerged that can be considered from an organization and software points of view. Better pharmacist's analysis of prescribing medication order within the CPOE system could possibly minimize duplication of antineoplasic drugs and the vital clinical impact associated with overdosage.
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