Dataset Information

Atezolizumab in a CoHort of pretreated, advanced, non-small cell lung cancer patients with rare HistologiCal SubtypEs (CHANCE trial).

ABSTRACT: Background:Although immunotherapy with immune-checkpoint inhibitors (ICIs) has profoundly changed the therapeutic scenario in the treatment of advanced non-small cell lung cancer (NSCLC), trials of ICIs only enrolled NSCLC patients with common histology. Atezolizumab was approved by the United States Food and Drug Administration (US FDA) in October 2016 and by the European Medicines Agency (EMA) in September 2017 for the treatment of patients with metastatic NSCLC whose disease progressed during or following platinum-containing chemotherapy, regardless of PD-L1 expression. Methods:We designed a single-arm, multicenter, two-stage phase II study and plan to enroll 43 patients. The primary objective of the study is to evaluate the antitumor activity of atezolizumab in advanced NSCLC patients with rare histology subtypes. Patients with prior atezolizumab or ICI treatment and with untreated, symptomatic, or progressing brain metastases will be excluded. The primary endpoint is disease control rate. Secondary objectives are toxicity and safety, overall response rate, progression-free survival, overall survival, and time to progression. Diagnosis of NSCLC with rare histology will be confirmed by central pathology revision, and will include: colloid carcinoma, fetal adenocarcinoma, non-endocrine large cell carcinoma, sarcomatoid carcinoma, salivary gland-type tumor, lymphoepithelioma-like carcinoma, and NUT-nuclear protein in testis carcinoma. Archival tumor tissue is required for correlative studies of PD-L1 expression on tumor cells and tumor infiltrating lymphocytes. Conclusions:Therapeutic options in NSCLC with rare histology subtypes, to be assessed in specifically designed trials, are an unmet need. This trial will help elucidate the role of atezolizumab as a viable option in this setting.

SUBMITTER: Gelsomino F

PROVIDER: S-EPMC7372524 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Atezolizumab in a CoHort of pretreated, advanced, non-small cell lung cancer patients with rare HistologiCal SubtypEs (CHANCE trial).

Gelsomino Francesco F Lamberti Giuseppe G Tiseo Marcello M Rocco Danilo D Pasello Giulia G Cecere Fabiana Letizia FL Chella Antonio A Grilli Giada G Mandruzzato Marcella M Tognetto Michele M Garassino Marina Chiara MC Macerelli Marianna M Novello Silvia S Roila Fausto F Colantonio Ida I Grossi Francesco F Fiorentino Michelangelo M Ardizzoni Andrea A

Therapeutic advances in medical oncology 20200720

<h4>Background</h4>Although immunotherapy with immune-checkpoint inhibitors (ICIs) has profoundly changed the therapeutic scenario in the treatment of advanced non-small cell lung cancer (NSCLC), trials of ICIs only enrolled NSCLC patients with common histology. Atezolizumab was approved by the United States Food and Drug Administration (US FDA) in October 2016 and by the European Medicines Agency (EMA) in September 2017 for the treatment of patients with metastatic NSCLC whose disease progresse ...[more]

PMID: 32733604

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Project description:BackgroundImmuno-radiotherapy may improve outcomes for patients with advanced solid tumors, although optimized combination modalities remain unclear. Here, we report the colorectal (CRC) cohort analysis from the SABR-PDL1 trial that evaluated the PD-L1 inhibitor atezolizumab in combination with stereotactic body radiation therapy (SBRT) in advanced cancer patients.MethodsEligible patients received atezolizumab 1200 mg every 3 weeks until progression or unmanageable toxicity, together with ablative SBRT delivered concurrently with the 2nd cycle (recommended dose of 45 Gy in 3 fractions, adapted upon normal tissue tolerance constraint). SBRT was delivered to at least one tumor site, with at least one additional measurable lesion being kept from the radiation field. The primary efficacy endpoint was one-year progression-free survival (PFS) rate from the start of atezolizumab. Sequential tumor biopsies were collected for deep multi-feature immune profiling.ResultsSixty pretreated (median of 2 prior lines) advanced CRC patients (38 men [63%]; median age, 59 years [range, 20-81 years]; 77% with liver metastases) were enrolled in five centers (France: n = 4, Spain: n = 1) from 11/2016 to 04/2019. All but one (98%) received atezolizumab and 54/60 (90%) received SBRT. The most frequently irradiated site was lung (n = 30/54; 56.3%). Treatment-related G3 (no G4-5) toxicity was observed in 3 (5%) patients. Median OS and PFS were respectively 8.4 [95%CI:5.9-11.6] and 1.4 months [95%CI:1.2-2.6], including five (9%) patients with PFS > 1 year (median time to progression: 19.2 months, including 2/5 MMR-proficient). Best overall responses consisted of stable disease (n = 38; 64%), partial (n = 3; 5%) and complete response (n = 1; 2%). Immune-centric multiplex IHC and RNAseq showed that SBRT redirected immune cells towards tumor lesions, even in the case of radio-induced lymphopenia. Baseline tumor PD-L1 and IRF1 nuclear expression (both in CD3 + T cells and in CD68 + cells) were higher in responding patients. Upregulation of genes that encode for proteins known to increase T and B cell trafficking to tumors (CCL19, CXCL9), migration (MACF1) and tumor cell killing (GZMB) correlated with responses.ConclusionsThis study provides new data on the feasibility, efficacy, and immune context of tumors that may help identifying advanced CRC patients most likely to respond to immuno-radiotherapy.Trial registrationEudraCT N°: 2015-005464-42; Clinicaltrial.gov number: NCT02992912.

Project description:ObjectiveAtezolizumab is becoming a significant therapy for non-small cell lung cancer (NSCLC), but its efficacy needs to be further improved. The aims of this study are to clarify the potency of atezolizumab-based therapy in advanced NSCLC patients with different clinical and molecular features, and to choose a better therapeutic regimen of atezolizumab to achieve more precise treatment in immunotherapy.MethodsRandomized clinical trials (RCTs) in the Cochrane Library, PubMed, Embase Science Direct, and Google Scholar, together with major oncology conferences that compared atezolizumab with chemotherapy-based treatment for individuals with advanced NSCLC published prior to February 2022, were searched. Studies, bias risk assessment, and data extraction were selected by two independent authors. We extracted the basic features of the included studies, together with the 95% confidence interval (CI) and hazard ratios (HRs), from all patients and subgroups. The combined treatment data were assessed using the inverse variance weighting method.ResultsSeven RCTs including 4,859 patients were included. Our meta-analysis findings indicated that atezolizumab substantially enhanced OS (HR 0.82; 95% CI, 0.77-0.88; p < 0.00001) and PFS (HR 0.72; 95% CI, 0.61-0.85; p < 0.0001) in patients with advanced NSCLC compared with chemotherapy-based treatment. Atezolizumab substantially enhanced OS in patients aged <65 years old and 65-74 years old, those with wild-type EGFR, those without liver metastases, active or previous smokers, white patients and those with TC3 or IC3, TC2/3 or IC2/3, TC1/2/3 or IC1/2/3, and TC0 and IC0, but not in patients aged ≥75 years, never smokers, those with liver metastases, those with EGFR mutant, Asians, Black or African Americans, or those with TC1/2 or IC1/2. Patients with advanced NSCLC who received atezolizumab showed OS improvement regardless of sex (male or female), histological type (non-squamous or squamous NSCLC), performance status (0 or 1), and line of treatment (1st-line therapy or ≥2nd-line therapy). Subgroup analysis revealed that male individuals, those with non-squamous NSCLC, those with PS 1, active or previous smokers, and those with wild-type EGFR, TC3 or IC3, and TC1/2/3 or IC1/2/3 achieved OS benefit from atezolizumab treatment not related to the treatment line and treatment regimen.ConclusionsAge group, smoking history, liver metastasis status, EGFR mutation status, race, and PD-L1 expression can be used to predict the potency of atezolizumab and provide a better treatment regimen for patients with advanced NSCLC to achieve accurate and personalized treatment.

Dataset Information

Atezolizumab in a CoHort of pretreated, advanced, non-small cell lung cancer patients with rare HistologiCal SubtypEs (CHANCE trial).

Publications

Atezolizumab in a CoHort of pretreated, advanced, non-small cell lung cancer patients with rare HistologiCal SubtypEs (CHANCE trial).

Similar Datasets

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