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1.
Clin Lung Cancer ; 25(2): 190-195, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38262770

RESUMO

INTRODUCTION: Despite several therapeutic efforts, lung cancer remains a highly lethal disease. Novel therapeutic approaches encompass immune-checkpoint inhibitors, targeted therapeutics and antibody-drug conjugates, with different results. Several studies have been aimed at identifying biomarkers able to predict benefit from these therapies and create a prediction model of response, despite this there is a lack of information to help clinicians in the choice of therapy for lung cancer patients with advanced disease. This is primarily due to the complexity of lung cancer biology, where a single or few biomarkers are not sufficient to provide enough predictive capability to explain biologic differences; other reasons include the paucity of data collected by single studies performed in heterogeneous unmatched cohorts and the methodology of analysis. In fact, classical statistical methods are unable to analyze and integrate the magnitude of information from multiple biological and clinical sources (eg, genomics, transcriptomics, and radiomics). METHODS AND OBJECTIVES: APOLLO11 is an Italian multicentre, observational study involving patients with a diagnosis of advanced lung cancer (NSCLC and SCLC) treated with innovative therapies. Retrospective and prospective collection of multiomic data, such as tissue- (eg, for genomic, transcriptomic analysis) and blood-based biologic material (eg, ctDNA, PBMC), in addition to clinical and radiological data (eg, for radiomic analysis) will be collected. The overall aim of the project is to build a consortium integrating different datasets and a virtual biobank from participating Italian lung cancer centers. To face with the large amount of data provided, AI and ML techniques will be applied will be applied to manage this large dataset in an effort to build an R-Model, integrating retrospective and prospective population-based data. The ultimate goal is to create a tool able to help physicians and patients to make treatment decisions. CONCLUSION: APOLLO11 aims to propose a breakthrough approach in lung cancer research, replacing the old, monocentric viewpoint towards a multicomprehensive, multiomic, multicenter model. Multicenter cancer datasets incorporating common virtual biobank and new methodologic approaches including artificial intelligence, machine learning up to deep learning is the road to the future in oncology launched by this project.


Assuntos
Produtos Biológicos , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Inteligência Artificial , Pesquisa Translacional Biomédica , Estudos Prospectivos , Estudos Retrospectivos , Leucócitos Mononucleares , Biomarcadores , Terapias em Estudo , Produtos Biológicos/uso terapêutico
2.
Clin Colorectal Cancer ; 22(4): 450-456.e1, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37657955

RESUMO

INTRODUCTION: Pseudomyxoma peritonei (PMP) is a rare, slow growing tumor, traditionally considered chemoresistant. The only curative approach is cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC). At disease relapse, or in patients with inoperable disease at diagnosis, no standard treatment has been defined, though nonrandomized series showed promising results with fluoropyrimidine-based regimens. PATIENTS AND METHODS: We conducted a prospective study in patients with relapsed or unresectable PMP and confirmed disease progression at baseline. Patients received MMC (7 mg/m2 every 6 weeks, up to a maximum of 4 cycles) plus metronomic capecitabine (625 mg/sqm/day b.i.d.) and bevacizumab (7.5 mg/kg every 3 weeks) until disease progression, unacceptable toxicity, or consent withdrawal. Primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), overall response rate according to RECIST v1.1 criteria, serum markers response and safety. RESULTS: Fifteen patients were included. At a median follow-up of 26.1 months (IQR, 17.7-49.6), median PFS was 17.9 months (95% CI, 11.0-NE), with 1-year PFS and OS rates of 73% and 87%. Safety profile was manageable, with only 13% G3/G4 treatment-related adverse events. CONCLUSION: Metronomic capecitabine, bevacizumab, and MMC are an active regimen in advanced and progressive PMP and favorably compares with historical series.


Assuntos
Neoplasias do Apêndice , Hipertermia Induzida , Neoplasias Peritoneais , Pseudomixoma Peritoneal , Humanos , Pseudomixoma Peritoneal/tratamento farmacológico , Pseudomixoma Peritoneal/patologia , Mitomicina/uso terapêutico , Bevacizumab/efeitos adversos , Capecitabina/efeitos adversos , Neoplasias Peritoneais/tratamento farmacológico , Estudos Prospectivos , Hipertermia Induzida/métodos , Progressão da Doença , Neoplasias do Apêndice/patologia
3.
Front Oncol ; 12: 902967, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35756673

RESUMO

Among the several next-generation tyrosine kinase inhibitors (TKIs) tested against uncommon EFGR alterations, poziotinib has been demonstrated to be a powerful agent for metastatic non-small-cell lung cancer (mNSCLC) with aberrations in HER2 exon 20, and FDA approval is being sought in the previously-treated population. Poziotinib has also shown activity in mNSCLC with aberrations in EGFR exon 20. Herein, we report the first published case of a patient affected by mNSCLC harbouring an EGFR exon 20 insertion (EGFRex20ins) mutation who achieved a complete response (CR) under treatment with poziotinib as part of the ZENITH20 trial. In January 2021, a former smoker 62-year-old female patient was diagnosed with relapse, after two surgeries and post-operative chemotherapy of mNSCLC, at liver and retroperitoneal nodes. Given the identification by Next Generation Sequencing (NGS) of EGFRex20ins mutation, she was enrolled in ZENITH20-cohort 5 trial, a phase 2 multicentre study aimed to assess the efficacy and safety of poziotinib in patients with EGFR or HER2 exon 20 insertion mutations. Poziotinib as first-line systemic therapy for metastatic disease was initiated at the end of January 2021 and administrated at the initial dosage of 8 mg orally twice daily (BID). The most common side effects from the beginning of the treatment included alopecia, macular skin rash, diarrhoea, xerostomia, and conjunctivitis. Due to these adverse events, poziotinib was discontinued during the first 3 months and then reduced to 6 mg orally BID in April 2021. After the dose de-escalation, the adverse events ameliorated, and the patient better tolerated the treatment without further interruption. Since the first reevaluation (after 4 weeks of therapy), the treatment with poziotinib resulted to be remarkably effective, with a partial response (PR) subsequently confirmed in May and July 2021. Then, in October 2021, a CT scan confirmed a CR, maintained with good tolerance at the last reevaluation in February 2022. Treatment is still ongoing at the same dosage. In this case, poziotinib has represented a successful and well-tolerated first-line treatment alternative to chemotherapy in this patient with EGFR exon 20 insertion mutated mNSCLC.

4.
Eur J Cancer ; 149: 235-248, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33820681

RESUMO

BACKGROUND: The treatment of metastatic non-small-cell lung cancer (mNSCLC) patients with EGFR/HER2 exon 20 insertion mutation (i-mut) remains an unmet clinical need. Poziotinib, a new generation tyrosine kinase inhibitor, is currently under investigation as a potential targeted therapy. This compassionate study of its use aims to describe the activity/toxicity of poziotinib in mNSCLC with EGFR/HER2-exon-20-i-mut. PATIENTS AND METHODS: NSCLC patients who were treated either with EGFR or HER2 exon 20-i-mut within an expanded access program were included in this study. Poziotinib (16 mg or less) was administrated orally quaque die (QD). The primary end-point was the overall response rate (ORR) assessed by central review using RECIST v1.1, and secondary end-points were median progression free survival (PFS), disease control rate (DCR), median overall survival (OS) and toxicity. RESULTS: The median age of all the 30 patients was 58 years (25-80 years), most of them were females (73%); ECOG 0-1 (83%), EGFR i-mut (73%) and pre-treated (83%). 73% started with poziotinib at a dose of 16 mg. At data cut-off, 22 of 33 patients (73%) experienced a progress in the disease and 12 of 30 (40%) died. Median PFS was 5.6 months (95% CI: 3.6-6.7 months) and the mOS 9.5 months (95% CI: 5.3 - not-reached months). The ORR was 30% (EGFR/HER2: 23/50%) and DCR 80%. G3 AEs were reported in 66% of the patients and were found with skin rash (50%), diarrhoea (17.6%), mucositis (7%) and paronychia (3%). G5, possibly associated with pneumonitis might also have occurred. CONCLUSIONS: Poziotinib exhibited effects in mNSCLC patients with EGFR/HER2-exon 20-i-mut. The toxicity rate was high leading to frequent dose interruption and reduction, thereby reducing mPFS in patients with good ORR/DCR. ZENITH20 trial is now being used to evaluate the low dose and new scheduled dose (e.g. bis in die (BID)).


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Mutagênese Insercional , Inibidores de Proteínas Quinases/administração & dosagem , Quinazolinas/administração & dosagem , Receptor ErbB-2/antagonistas & inibidores , Receptor ErbB-2/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/secundário , Ensaios de Uso Compassivo , Progressão da Doença , Receptores ErbB/genética , Éxons , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/efeitos adversos , Quinazolinas/efeitos adversos , Fatores de Tempo
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