Small-molecule inhibitors, immune checkpoint inhibitors, and more: FDA-approved novel therapeutic drugs for solid tumors from 1991 to 2021

Journal of Hematology & Oncology, Год журнала: 2022, Номер 15(1)

Опубликована: Окт. 8, 2022

Abstract The United States Food and Drug Administration (US FDA) has always been a forerunner in drug evaluation supervision. Over the past 31 years, 1050 drugs (excluding vaccines, cell-based therapies, gene therapy products) have approved as new molecular entities (NMEs) or biologics license applications (BLAs). A total of 228 these were identified cancer therapeutics cancer-related drugs, 120 them classified therapeutic for solid tumors according to their initial indications. These evolved from small molecules with broad-spectrum antitumor properties early stage monoclonal antibodies (mAbs) antibody‒drug conjugates (ADCs) more precise targeting effect during most recent decade. extended indications other malignancies, constituting treatment system monotherapy combined therapy. However, available targets are still mainly limited receptor tyrosine kinases (RTKs), restricting development drugs. In this review, summarized indications, characteristics, functions. Additionally, RTK-targeted therapies immune checkpoint-based immunotherapies also discussed. Our analysis existing challenges potential opportunities may advance tumor future.

Язык: Английский

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Uncommon EGFR Compound Mutations in Non-Small Cell Lung Cancer (NSCLC): A Systematic Review of Available Evidence

Current Oncology, Год журнала: 2022, Номер 29(1), С. 255 - 266

Опубликована: Янв. 9, 2022

Compound epidermal growth factor receptor (EGFR) mutations represent a heterogeneous subgroup of non-small cell lung cancer (NSCLC) patients with uncommon EGFR mutations. We conducted systematic review to investigate the available data on this patients’ subgroup. Overall, we found high heterogeneity in incidence compound (4–26% total mutant cases), which is dependent different testing methods adopted and specific considered. In addition, relative distinct subclasses identified reported extreme variability studies. Preclinical clinical data, excluding de novoEGFR exon 20 p.T790M mutations, show good responses tyrosine kinase inhibitors (TKIs) (combined common mutations: response rate (RR) ≥ 75% either first- or second-generation TKIs; combined plus uncommon: RR 40–80% 100% first-generation TKIs afatinib, respectively; 20–70%, ~80% ~75% TKIs, afatinib osimertinib, respectively). are consistent supporting use treating taking into account sensitivity profile accompanying for selecting most adequate TKI individual patients.

Язык: Английский

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Clinical Outcomes of Afatinib Versus Osimertinib in Patients With Non-Small Cell Lung Cancer With Uncommon EGFR Mutations: A Pooled Analysis

The Oncologist, Год журнала: 2023, Номер 28(6), С. e397 - e405

Опубликована: Апрель 28, 2023

Abstract Background The purpose of this analysis was to investigate the effectiveness afatinib compared that osimertinib in patients with non-small cell lung cancer (NSCLC) who harbored uncommon epidermal growth factor receptor (EGFR) mutations. Methods A PubMed database-based literature review conducted retrieve related studies. Patients harboring EGFR mutations besides deletion exon 19 (19del) and point mutation L858R were included analysis. primary outcome events objective response rate (ORR) progression-free survival (PFS). Propensity score matching (PSM) at a ratio 1:1 used between groups control confounding factors. Uncommon categorized into 4 groups: insertion 20 (ex20ins), non-ex20ins single mutations, compound 19del or L858R, without L858R. Results After PSM, 71 either group matched. had an ORR 60.6%, slightly higher than group’s (50.3%), difference not statistically significant (P = .610). However, showed significantly superior PFS benefit (11.0 vs. 7.0 months, P .044). In addition, yield best PFS, following treatment (ORR: 76.7%, mPFS: 14.1 months) 68.8%, 15.1 months). Moreover, there no terms cohort treated osimertinib, regardless whether brain metastases. Conclusions Both displayed favorable clinical activities toward Afatinib more profound durable although efficacy advantage observed.

Язык: Английский

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Overview on Therapeutic Options in Uncommon EGFR Mutant Non-Small Cell Lung Cancer (NSCLC): New Lights for an Unmet Medical Need

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(10), С. 8878 - 8878

Опубликована: Май 17, 2023

The majority of epidermal growth factor receptor (EGFR) mutations (85-90%) are exon 19 deletions and L858R point 21, characterized by high sensitivity to EGFR-tyrosine kinase inhibitors (TKIs). Less is known about uncommon (10-15% EGFR mutations). predominant mutation types in this category include 18 mutations, 21 L861X, 20 insertions, S768I. This group shows a heterogeneous prevalence, partly due different testing methods the presence compound which some cases can lead shorter overall survival TKIs compared simple mutations. Additionally, EGFR-TKI may also vary depending on specific tertiary structure protein. best strategy remains uncertain, data EGFR-TKIs efficacy based few prospective retrospective series. Newer investigational agents still under study, there no other approved treatments targeting Defining treatment option for patient population an unmet medical need. objective review evaluate existing outcomes, epidemiology, clinical characteristics lung cancer patients with rare focus intracranial activity response immunotherapy.

Язык: Английский

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Non-small cell lung cancer: an update on emerging EGFR-targeted therapies

Expert Opinion on Emerging Drugs, Год журнала: 2024, Номер 29(2), С. 139 - 154

Опубликована: Апрель 2, 2024

Current research in EGFR-mutated NSCLC focuses on the management of drug resistance and uncommon mutations, as well opportunity to extend targeted therapies' field action earlier stages disease.

Язык: Английский

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Discovery of mobocertinib, a new irreversible tyrosine kinase inhibitor indicated for the treatment of non-small-cell lung cancer harboring EGFR exon 20 insertion mutations

Medicinal Chemistry Research, Год журнала: 2022, Номер 31(10), С. 1647 - 1662

Опубликована: Сен. 1, 2022

Язык: Английский

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Tyrosine Kinase Inhibitor Activity in Patients with NSCLC Harboring Uncommon EGFR Mutations: A Retrospective International Cohort Study (UpSwinG)

The Oncologist, Год журнала: 2022, Номер 27(4), С. 255 - 265

Опубликована: Янв. 27, 2022

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) are standard of care for patients with EGFR mutation-positive non-small-cell lung cancer (NSCLC) common mutations (Del19 or L858R); however, 7%-23% NSCLC tumors harbor uncommon mutations. These highly heterogeneous, and developments in detection techniques helping to identify little no clinical data.

Язык: Английский

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From Rarity to Reality: Osimertinib's Promising Horizon in Treating Uncommon EGFR Mutations in Non-Small Cell Lung Cancer

Clinical Cancer Research, Год журнала: 2024, Номер 30(15), С. 3128 - 3136

Опубликована: Май 20, 2024

In the realm of advanced non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) therapy with tyrosine kinase inhibitors (TKI), addressing optimal treatment for uncommon EGFR mutations like G719X in exon 18, S768I 20, and L861Q 21 remains a pivotal yet challenging frontier. Contrary to well-established efficacy EGFR-TKIs common mutations, these alterations pose unmet medical needs due lack comprehensive evidence. While afatinib, second-generation EGFR-TKI, has received FDA approval patients was based on post-hoc analysis randomized clinical trials. Recent developments include multiple trials investigating both second- third-generation mutations. A noteworthy example is prospective phase II trial osimertinib including landmark UNICORN study, which shown promising results treating Despite various reports afatinib appropriate use TKIs unclear. This review aims consolidate findings from latest focused outlining variations therapeutic specific genetic mutation. By synthesizing findings, we aim guide oncologists toward more informed decisions employing NSCLC other than 20 insertion. Additionally, explore potential strategies tailored patient populations address challenges posed by

Язык: Английский

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Management of Treatment Resistance in Patients With Advanced Epidermal Growth Factor Receptor–Mutated Lung Cancer: Personalization, Parsimony, and Partnership

Journal of Clinical Oncology, Год журнала: 2024, Номер 42(11), С. 1215 - 1221

Опубликована: Фев. 27, 2024

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation followed by a description of diagnostic and management challenges, review relevant literature, summary authors’ suggested approaches. goal this help readers better understand how apply results key studies, including those Clinical , patients seen their own practice. Patients with epidermal growth factor receptor ( EGFR)–mutated advanced non–small-cell lung cancer represent distinct subgroup individuals who can experience initially tolerable durable effects first-line EGFR-directed tyrosine kinase inhibitors. Unfortunately, acquired treatment resistance progression within CNS are inevitable during disease course present challenging transition care continuum. Next-line therapies generally require combinations drugs afford nuanced differences outcomes relative experience, toxicity profile, quality life. Therapeutic stratification modulation thus further personalization partnership identify clinical, molecular, human-specific factors best guide optimal care.

Язык: Английский

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Co-occurring EGFR p.E709X Mutation Mediates Primary Resistance to the Third-Generation EGFR-TKIs in EGFR p.G719X-Mutant Patients with Advanced NSCLC

Clinical Cancer Research, Год журнала: 2024, Номер 30(12), С. 2636 - 2646

Опубликована: Апрель 5, 2024

Abstract Purpose: The current National Comprehensive Cancer Network (NCCN) guidelines recommend afatinib or osimertinib as the preferred first-line treatment strategy for patients with advanced NSCLC harboring EGFR p.G719X mutation. However, in absence of head-to-head trials comparing p.G719X-mutant patients, it is unclear which regimen option. Experimental Design: A large cohort 4,228 treatment-naïve lung cancer who underwent targeted next-generation sequencing (NGS) testing was screened multicenter involving 68 and NGS profiling retrospectively enrolled to evaluate clinical responses (n = 37) third-generation EGFR-TKIs 31). Ba/F3 cells stably expressing p.G719A mutation were created investigate response vitro. Results: Concurrent p.E709X mutations, being most frequent co-occurring (∼30%), exerted a detrimental effect on outcomes treated EGFR-TKI [G719X/E709X vs. G719X; objective rate (ORR): 0.00% 47.62%, P < 0.001; mPFS: 7.18 14.2 months, 0.04, respectively]. Conversely, no significant difference found efficacy between p.G719X/E709X (G719X/E709X ORR: 71.43% 56.67%, 0.99; 14.7 15.8 0.69, respectively). In vitro experiments elucidated resistant drug sensitivity poor inhibition phosphorylation p.G719A/E709K upon treatment. Conclusions: Co-occurring mediated primary resistance but remained sensitive afatinib. personalized should be undertaken based coexisting status.

Язык: Английский

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