Search

Treatment of advanced non-smallcell lung cancer is usually based on several lines of therapy separated by treatment-free intervals, in which each new line is started when tumor progression is detected. The maintenance strategy consists of continuing an appropriate, well-tolerated treatment immediately after the end of first-line chemotherapy, in order to maintain the initial therapeutic benefit and to avoid rapid clinical deterioration that would rule out further treatment. Maintenance can use either a non-platinum component of induction chemotherapy defining 'continuation maintenance' or initiation of a new agent consisting in 'switch maintenance'. Clinical trials show that maintenance therapy with pemetrexed or erlotinib provides a significant clinical benefit in terms of disease control and survival. Maintenance therapy is an important option in first-line treatment of non-small cell lung cancer but more reliable criteria is needed to identify the patientsmost likely to benefit from either continuation or switch maintenance. [ABSTRACT FROM AUTHOR]

Summary: From 5 March 2001 to 19 October 2001, outbreaks of broncho-alveolar lavage (BAL) contamination with Enterobacteraceae were detected in our 700-bed institution. We report the investigation of these outbreaks. A case was defined as the occurrence of pairs of specific Enterobacteraceae in BAL specimens among any patients who underwent bronchoscopy in the respiratory unit during the period of the outbreak. Contamination was identified in 117 BAL samples during three outbreaks among 418 patients, and was associated with bronchoscopes 11 and 12 (P<0.001). The other five devices in use were not linked with the outbreaks. During the first outbreak, particular pairs of micro-organisms were associated with a specific bronchoscope (Klebsiella pneumoniae/Proteus vulgaris with bronchoscope 11, and Morganella morganii/Proteus mirabilis with bronchoscope 12). Cultures of sputa from two patients also yielded M. morganii some days after bronchoscopic examination. Isolates from contaminated BAL samples and bronchoscope 11 had similar patterns by pulsed-field gel electrophoresis. No further cases occurred after removal of the implicated bronchoscopes. No deficiencies in disinfection procedures were detected and the source of contamination was found to be a loose port of the biopsy channel of the bronchoscope. Our findings underscore the urgent need to test bronchoscopic samples regularly and to improve the design and structure of bronchoscopes. [Copyright &y& Elsevier]

• TKI have revolutionized the course of advanced NSCLC with EGFR common mutation. • Tumor heterogeneity and acquired resistance mechanisms are unavoidable limits. • Multiple novel treatment strategies based on various combinations have emerged. • Treatment strategy should be based on the clinical and biological profile. • Taking patients preferences into account is essential in the therapeutic strategy. Common EGFR gene mutations (exon 19 deletion and L858R in exon 21) are the most frequent cause of actionable genomic alterations in non-small cell lung cancer (NSCLC) patients. The introduction of EGFR tyrosine kinase inhibitors (TKIs) as 1st-line treatment of advanced stages of the disease has changed the natural history of the disease and extended survival rates, establishing third generation TKIs as a new standard of frontline treatment. Nonetheless, the prolongation of overall survival remains modest, as multiple escape pathways and tumor increasing heterogeneity inevitably develop over time. Several strategies are currently developed to improve these patients' outcome: prevent the emergence of resistance mechanisms by therapeutic combinations introduced from the first line, act on the residual disease at the time of maximum response to 1st line treatment, develop therapeutic strategies at the time of acquired resistance to TKIs, either dependent on the resistance mechanisms, or agnostic of the resistance pathways. Recent advancements in treatment combinations have shown promising results in prolonging progression-free survival, but often at the cost of more severe side effects in comparison with the current standard of care. These emerging new treatment options open up possibilities for diverse therapeutic sequences in the management of advanced NSCLC depending on common EGFR mutations. The impact on the disease natural history, the patients' survival and quality of life is not yet fully understood. In this review, we propose an overview of published and forthcoming advances, and a management algorithm considering the different first-line options, integrating the clinical and biological parameters that are critical to clinicians' decision-making process. [ABSTRACT FROM AUTHOR]

Following the approval of the first antibody–drug conjugates (ADCs) in the early 2000s, development has increased dramatically, with 14 ADCs now approved and >100 in clinical development. In lung cancer, trastuzumab deruxtecan (T-DXd) is approved in human epidermal growth factor receptor 2 (HER2)-mutated, unresectable or metastatic non-small-cell lung cancer, with ADCs targeting HER3 (patritumab deruxtecan), trophoblast cell-surface antigen 2 [datopotamab deruxtecan and sacituzumab govitecan (SG)] and mesenchymal–epithelial transition factor (telisotuzumab vedotin) in late-stage clinical development. In breast cancer, several agents are already approved and widely used, including trastuzumab emtansine, T-DXd and SG, and multiple late-stage trials are ongoing. Thus, in the coming years, we are likely to see significant changes to treatment algorithms. As the number of available ADCs increases, biomarkers (of response and resistance) to better select patients are urgently needed. Biopsy sample collection at the time of treatment selection and incorporation of translational research into clinical trial designs are therefore critical. Biopsy samples taken peri- and post-ADC treatment combined with functional genomics screens could provide insights into response/resistance mechanisms as well as the impact of ADCs on tumour biology and the tumour microenvironment, which could improve understanding of the mechanisms underlying these complex molecules. Many ADCs are undergoing evaluation as combination therapy, but a high bar should be set to progress clinical evaluation of any ADC-based combination, particularly considering the high cost and potential toxicity implications. Efforts to optimise ADC dosing/duration, sequencing and the potential for ADC rechallenge are also important, especially considering sustainability aspects. The ETOP IBCSG Partners Foundation are driving strong collaborations in this field and promoting the generation/sharing of databases, repositories and registries to enable greater access to data. This will allow the most important research questions to be identified and prioritised, which will ultimately accelerate progress and help to improve patient outcomes. • As the number of available ADCs increases, biomarkers are required to optimise treatment algorithms and patient selection. • Combination therapy of ADCs should be scientifically driven and studied in biomarker-driven trials of enriched populations. • Efforts to optimise ADC treatment duration, sequencing and the potential for ADC rechallenge are essential. • In clinical trials, biopsy sample collection and translational research are critical to improve our understanding of ADCs. • Effective collaborations are required to accelerate progress, which will ultimately help improve patient outcomes. [ABSTRACT FROM AUTHOR]

Background In 2013, the French National Cancer Institute initiated the AcSé program to provide patients with secure access to targeted therapies outside of their marketed approvals. Efficacy and safety was then assessed using a two-stage Simon phase II trial design. When the study design was designed, crizotinib was approved only as monotherapy for adults with anaplastic lymphoma kinase plus non-small-cell lung cancers (NSCLC). Patients and methods Advanced NSCLC patients with c-MET ≥6 copies, c-MET -mutated, or ROS-1 -translocated tumours were enrolled in one of the three cohorts. Patients were treated with crizotinib 250 mg twice daily. Efficacy was assessed using the objective response rate (ORR) after two cycles of crizotinib as primary outcome. Secondary outcomes included disease control rate at four cycles, best ORR, progression-free survival, overall survival, and drug tolerance. Results From August 2013 to March 2018, 5606 patients had their tumour tested for crizotinib targeted molecular alterations: 252 patients had c-MET ≥6 copies, 74 c-MET -mutation, and 78 ROS-1 -translocated tumour. Finally, 25 patients in the c-MET ≥6 copies cohort, 28 in the c-MET -mutation cohort, and 37 in the ROS-1 -translocation cohort were treated in the phase II trial. The ORR was 16% in the c-MET ≥6 copies cohort, 10.7% in the mutated, and 47.2% in the ROS-1 cohort. The best ORR during treatment was 32% in the c-MET -≥6 copies cohort, 36% in the c-MET -mutated, and 69.4% in the ROS-1 -translocation cohort. Safety data were consistent with that previously reported. Conclusions Crizotinib activity in patients with ROS1 -translocated tumours was confirmed. In the c-MET -mutation and c-MET ≥6 copies cohorts, despite insufficient ORR after two cycles of crizotinib, there are signs of late response not sufficient to justify the development of crizotinib in this indication. The continued targeting of c-MET with innovative therapies appears justified. Clinical trial number NCT02034981. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses the therapeutic effects of rituximab in paraneoplastic treatment-refractory Morvan syndrome patient associated with anti-contactin-associated protein-2 (CASPR2) antibodies.