Efficacy of Immune Checkpoint Inhibitors Alone or in Combination With Chemotherapy in NSCLC Harboring ERBB2 Mutations

Saalfeld, Felix C.; Wenzel, Carina; Christopoulos, Petros; Merkelbach‐Bruse, Sabine; Reissig, Timm M.; Laßmann, Silke; Thiel, Steffen; Stratmann, Jan; Marienfeld, Ralf; Berger, Johannes; Desuki, Alexander; Velthaus, Janna-Lisa; Kauffmann-Guerrero, Diego; Michels, Sebastian; Herold, Thomas; Kramer, Michael; Herold, Sylvia; Tufman, Amanda; Loges, Sonja; Alt, Jürgen August; Joosten, Maria; Schmidtke-Schrezenmeier, Gerlinde; Sebastian, Martin; Stephan-Falkenau, Susann; Waller, Christiane; Wiesweg, Marcel; Wolf, Jürgen; Thomas, Michael; Aust, Daniela E.; Wermke, Martin

doi:10.1016/j.jtho.2021.06.025

Cited by 37 publications

(32 citation statements)

References 11 publications

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“…A phase II study of pyrotinib with apatinib as second-line therapy in HER2 amplification or activating mutations had the overall ORR and DCR of 45.5 and 93.9%, respectively [98]. The retrospective study of ICI combined with chemotherapy as first-line showed an ORR of 52% and an mPFS of 6 months in HER2-mutated NSCLC [99]. HER2 exon 16-skipping (HER2D16) as a novel mechanism confers osimertinib resistance, and afatinib with osimertinib could inhibit tumor cell growth and signal in vitro [52,53].…”

Section: Her2-mediated Resistancementioning

confidence: 99%

Resistance mechanisms to osimertinib and emerging therapeutic strategies in nonsmall cell lung cancer

Zeng

Tian

et al. 2021

Current Opinion in Oncology

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Purpose of reviewThis review aims to introduce the resistance mechanisms to osimertinib, discuss the therapeutic strategies, and make clinical updates in overcoming resistance to osimertinib. Recent findingsOsimertinib has shown favorable efficacy on second-line and first-line treatments in EGFR-mutant advanced nonsmall cell lung cancer (NSCLC). However, the presence of primary and acquired resistance to osimertinib restricts its clinical benefits. The primary resistance mainly consists of BIM deletion polymorphism and EGFR exon 20 insertions. Meanwhile, the heterogeneous mechanisms of acquired resistance include EGFR-dependent (on-target) and EGFR-independent (off-target) mechanisms. EGFR C797S mutation, MET amplification, HER2 amplification, and small cell lung cancer transformation were identified as frequent resistance mechanisms. Recently, more novel mechanisms, including rare EGFR point mutations and oncogenic fusions, were reported. With the results of completed and on-going clinical trials, the emerging therapeutic strategies of postosimertinib progression are summarized.

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Section: Her2-mediated Resistancementioning

confidence: 99%

Resistance mechanisms to osimertinib and emerging therapeutic strategies in nonsmall cell lung cancer

Zeng

Tian

et al. 2021

Current Opinion in Oncology

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“…The ORR, DCR and median PFS were 38.5%, 84.6% and 7.4 months, respectively ( 96 ). Additionally, results from another study demonstrated that the ORR, median PFS, and one-year OS rate of ICIs combined with chemotherapy for treatment-naive HER2-mutant NSCLC were 52%, 6 months and 88%, respectively ( 97 ). Tian et al.…”

Section: Targeting Her2 In Nsclc: Perplexity and Progressmentioning

confidence: 99%

HER2-Altered Non-Small Cell Lung Cancer: Biology, Clinicopathologic Features, and Emerging Therapies

2022

Front. Oncol.

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Multiple oncogenic molecular alterations have been discovered that serve as potential drug targets in non-small cell lung cancer (NSCLC). While the pathogenic and pharmacological features of common targets in NSCLC have been widely investigated, those of uncommon targets are still needed to be clarified. Human epidermal growth factor receptor 2 (HER2, ERBB2)-altered tumors represent a highly heterogeneous group of diseases, which consists of three distinct situations including mutation, amplification and overexpression. Compared with breast and gastric cancer, previous studies have shown modest and variable results of anti-HER2 treatments in lung cancers with HER2 aberrations, thus effective therapies in these patients represent an unmet medical need. By far, encouraging efforts towards novel treatment strategies have been made to improve the clinical outcomes of these patients. In this review, we describe the biological and clinicopathological characteristics of HER2 alterations and systematically sum up recent studies on emerging therapies for this subset of patients.

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“…Consistently, a recent study suggested that first-line chemo-immunotherapy for HER2 -mutated NSCLC may achieve response rates comparable to those of unselected patients with NSCLC, with an ORR of 52.4% and a median PFS of 6.0 months. 64 At the time of progressive disease, these patients should receive a HER2-targeted drug as second-line therapy, which has been demonstrated to achieve better outcomes when compared to historical data of second-line chemotherapy used for unselected patients with NSCLC. On the other hand, ICI as monotherapy (in case of no prior immune-checkpoint inhibition) should be reserved as third-line treatment given the response rate lower than 10% that has been generally observed in retrospective studies.…”

Section: Her2 Exon 20 Insertion Mutationsmentioning

confidence: 99%

Advanced non-small-cell lung cancer: how to manage EGFR and HER2 exon 20 insertion mutation-positive disease

Metro¹,

Giglio²,

Ricciuti³

et al. 2022

DIC

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EGFR exon 20 insertion mutations (Ex20ins) and HER 2 mutations characterize an oncogene-addicted subtype of non-small-cell lung cancer (NSCLC) typically associated with a never or light smoking history, female sex, and adenocarcinoma histology. Nevertheless, Ex20ins-mutant and HER 2-mutant advanced NSCLCs are still difficult to treat for various reasons. First, there is a need for sophisticated diagnostic tools (e.g. next-generation sequencing) that could allow the identification of these relatively rare molecular drivers. Second, highly active targeted drugs that might support a significant change in patients’ prognosis when used as first-line therapy are required. In fact, although a few targeted drugs have so far demonstrated antitumour activity for these patients, mainly selective human epidermal receptor-tyrosine kinase inhibitors such as poziotinib and mobocertinib (for both molecular alterations), monoclonal antibodies such as amivantamab (for Ex20ins), and antibody–drug conjugates such as trastuzumab deruxtecan (for HER2 mutants), they are mostly confined for clinical use in pretreated patients. Finally, Ex20ins-targeted or HER2-targeted drugs might be difficult to access in different countries or regions worldwide. In the present review, we provide a concise but comprehensive summary of the challenges that lie ahead as we move towards personalized treatment of Ex20ins-mutant and HER2 -mutant advanced NSCLC, also suggesting a treatment algorithm that could be followed for patients with these genetic aberrations.

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Efficacy of Immune Checkpoint Inhibitors Alone or in Combination With Chemotherapy in NSCLC Harboring ERBB2 Mutations

Cited by 37 publications

References 11 publications

Resistance mechanisms to osimertinib and emerging therapeutic strategies in nonsmall cell lung cancer

Resistance mechanisms to osimertinib and emerging therapeutic strategies in nonsmall cell lung cancer

HER2-Altered Non-Small Cell Lung Cancer: Biology, Clinicopathologic Features, and Emerging Therapies

Advanced non-small-cell lung cancer: how to manage EGFR and HER2 exon 20 insertion mutation-positive disease

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