Clinical significance of ROS1 5' deletions detected by FISH and response to crizotinib

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Phase 2 study of NAB-paclitaxel in SensiTivE and refractory relapsed small cell lung cancer (SCLC) (NABSTER TRIAL)

Background: Despite sensitivity to first-line chemotherapy, most small-cell lung cancer (SCLC) patients relapse. In this setting, topotecan demonstrated modest activity with significant toxicity. Paclitaxel was also active. This study was designed to evaluate activity and safety of nab-paclitaxel in relapsed SCLC. Methods: In this multicentre prospective Phase 2 trial, patients with refractory or sensitive SCLC progressed to first-line platinum-based chemotherapy received nab-paclitaxel 100 mg/smq on days 1, 8, 15 every 4 weeks up to six cycles, progressive disease or intolerable toxicity. Primary endpoint was investigator-assessed objective tumour response. Secondary endpoints were toxicity, progression-free survival (PFS) and overall survival (OS). Results: Of the 68 patients treated, partial response was 8% in the refractory cohort and 14% in the sensitive cohort. Most common toxicities of any grade were fatigue (54%), anaemia (38%), neutropenia (29%), leukopenia (26%) and diarrhoea (21%). Median PFS was similar in both refractory (1.8 months) and sensitive cohorts (1.9 months), while median OS was longer in sensitive one (6.6 versus 3.6 months). Conclusions: Although nab-paclitaxel has shown some modest anti-tumour activity in relapsed SCLC, associated with a favourable toxicity profile, the primary end-point of the study was not met. Clinical Trial registration: Clinical Trial registration number is ClinicalTrials.gov Identifier: NCT03219762

Detection of EGFR-Activating and T790M Mutations Using Liquid Biopsy in Patients With EGFR-Mutated Non–Small-Cell Lung Cancer Whose Disease Has Progressed During Treatment With First- and Second-Generation Tyrosine Kinase Inhibitors: A Multicenter Real-Life Retrospective Study

Epidermal growth factor receptor T790M detection using liquid biopsy was evaluated in a real-life setting in 120 advanced non–small-cell lung cancer patients whose disease had progressed during first- or second-generation tyrosine kinase inhibitors. The T790M detection rate was 25.8% using liquid biopsy and 49.2% after tissue rebiopsy. Liquid biopsies performed before disease progression according to Response Evaluation Criteria In Solid Tumors were all negative for T790M and T790M positivity was higher in cases of extrathoracic metastatic sites

Immunotherapy-refractory, EGFR overexpressing metastatic porocarcinoma responding to cetuximab

No abstract availabl

Cardiac Toxicity From Afatinib in EGFR-Mutated NSCLC: A Rare But Possible Side Effect

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Effective retreatment with osimertinib in CNS-relapsed epidermal growth factor receptor-mutant non-small cell lung cancer patient following resection and adjuvant osimertinib

For years, adjuvant chemotherapy has been the only standard treatment for resected non-small cell lung cancer patients (NSCLC), offering a dismal survival improvement at 5 years. Following the outstanding results of the recent ADAURA trial, osimertinib has become a new standard treatment for resected epidermal growth factor receptor (EGFR)-mutant non-squamous NSCLC, regardless of the administration of chemotherapy. For patients whose disease relapses after completion of the adjuvant therapy, there is no consensus about the optimal treatment. Herein, we report the case of a 74-year-old woman diagnosed with stage IIIA non-squamous NSCLC, harboring the EGFR p.L858R mutation. After complete tumor resection, the patient received adjuvant chemotherapy with cisplatin and vinorelbine, followed by osimertinib 80 mg daily for 3 years within the ADAURA trial. Brain disease relapse was documented 18 months after treatment completion by computed tomography scans. The patient was then retreated with osimertinib obtaining a deep intracranial partial response, which is still lasting after 21 months. The retreatment with osimertinib in patients whose disease relapsed following adjuvant therapy with the third-generation EGFR inhibitor might be a valid option, especially in patients with intracranial disease relapse. Studies are warranted to confirm this finding and to define the impact of the disease-free interval in this regard

Clinical significance of ROS1 5\u2019 deletions in non-small cell lung cancer

Patients harboring rearrangements of the ROS1 gene are eligible for first-line therapy with Crizotinib, which represents the best available treatment option. Diagnostic criteria, based on break-apart fluorescence in situ hybridization, were mirrored from ALK by analogy and include tumors with 5' deletions. However, the probability of response to Crizotinib in patients with 5' deletion in ROS1 is unknown given the rarity of this condition

Non-small-cell lung cancer: how to manage RET-positive disease

Targeted therapy has dramatically changed the history and outcomes of oncogene-addicted non-small-cell lung cancer (NSCLC). RET rearrangements are typically observed in about 1–2% of NSCLC, resulting in constitutive activation of downstream signalling pathways commonly involved in cell growth and survival. RET-positive NSCLCs are generally associated with young age, non-smoking history, a high rate of brain metastases at diagnosis and an immunologically ‘cold’ tumour microenvironment. Multi-kinase inhibitors, such as cabozantinib, lenvatinib and vandetanib, showed limited efficacy but significant toxicity mainly linked to off-target effects. In contrast, two RET-selective tyrosine kinase inhibitors (TKIs), selpercatinib and pralsetinib, demonstrated high response rates and manageable safety profiles, and have received FDA approval for the treatment of advanced RET-positive NSCLC regardless of previous lines of treatment. Despite the initial high response rate to RET-TKIs, most patient inevitably develop disease progression due to acquired resistance mechanisms by both on-target or off-target mechanisms. To date, new potent and selective next-generation RET-TKIs are currently being evaluated in ongoing clinical trials in order to overcome resistance and improve efficacy and blood–brain barrier crossing. Genomic recharacterization at progression could help guide treatment choice or enrolment in clinical trials of specific next-generation RET inhibitors. Here, we review the biology, clinicopathological characteristics, targeted therapies and mechanisms of resistance of advanced NSCLC harbouring RET fusions to provide treatment guidance for these patients

Overcoming Primary Resistance to PD-1 Inhibitor With Anti\u2013PD-L1 Agent in Squamous-Cell NSCLC: Case Report

Clinical Practice Points \u2022Immune checkpoint inhibitors (ICI) have changed the treatment landscape of advanced non\u2013small-cell lung cancer, as they have shown their superiority to chemotherapy in the first-line setting in tumors having programmed death ligand 1 (PD-L1) expression 65 50% and in patients with pretreated disease, regardless of PD-L1 expression. \u2022 The efficacy and safety of ICI rechallenge in those patients whose disease failed to respond to a prior treatment with these agents remain unclear. \u2022 We report the case of a 79-year-old woman, a smoker, with locally advanced, TP53-mutated squamous non\u2013small-cell lung cancer, whose disease responded to an anti\u2013PD-L1 agent despite having experienced disease progression during a prior anti\u2013programmed cell death 1 treatment that followed first-line chemoradiotherapy. The anti\u2013PD-L1 therapy was still ongoing after 9 months. \u2022 Our case suggests that ICI rechallenge could be safe and effective, even in a subpopulation of patients with disease that did not respond to prior ICI therapy