Hype or hope – Can combination therapies with third-generation EGFR-TKIs help overcome acquired resistance and improve outcomes in EGFR-mutant advanced/metastatic NSCLC?

Papini, Filippo; Sundaresan, Janani; Leonetti, Alessandro; Tiseo, Marcello; Rolfo, Christian; Peters, Godefridus J.; Giovannetti, Elisa

doi:10.1016/j.critrevonc.2021.103454

Cited by 19 publications

(13 citation statements)

References 234 publications

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“…The reason for the poor response to osimertinib in our case remains unclear. The reported potential mechanisms of resistance to osimertinib include the emergence of on-target resistance mutation such as EGFR C797S, bypass pathway activation such as MET amplification, or histologic small cell transformation (8,100,101,104). Timely rebiopsies with comprehensive genomic profiling following disease progression on osimertinib therapy may be helpful for unraveling the resistance mechanisms (8).…”

Section: Discussionmentioning

confidence: 99%

“…Chemotherapy, immunotherapy, and antiangiogenic therapy, either alone or in combination, may be considered for further treatment (100). Also, the combination of EGFR-TKIs with other therapeutic agents such as chemotherapy or vascular endothelial growth factor (VEGF) inhibitors has emerged as a potential therapeutic approach in the first-line setting to overcome EGFR-TKI resistance (101,104). Several clinical trials are currently exploring the role of combination approaches with osimertinib (105), which may provide critical information to inform future treatment practice.…”

Section: Discussionmentioning

confidence: 99%

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Gastric Metastasis of Primary Lung Cancer: Case Report and Systematic Review With Pooled Analysis

Tang

Liu

et al. 2022

Front. Oncol.

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BackgroundGastric metastasis from lung cancer (GMLC) is a rare occurrence. The clinicopathological characteristics, outcomes, and prognostic factors remain largely elusive.MethodsWe conducted a systematic review on case reports and case series of GMLC by scanning MEDLINE, Embase, and ISI Web of Knowledge. Data involving the clinicopathological features, treatment, and outcomes were extracted and analyzed. Survival analysis was performed using Kaplan–Meier method. The Cox proportional hazards regression model was used to identify potential prognostic factors associated with survival. Furthermore, a case of metastatic gastric adenocarcinoma of pulmonary origin with epidermal growth factor receptor (EGFR) L858R+T790M mutation was also described and included.ResultsSeventy-eight records involving 114 cases (including ours) were finally included. The median age on admission was 65 years with a male predominance of 79.8%. Lung adenocarcinoma (42.1%), located in the right upper lobe (30.3%), was the most frequent primary tumor. Bleeding (36.7%) and abdominal pain (35.8%) were the two most common symptoms. Endoscopically, gastric lesions were typically presented as elevated lesions with or without volcano-like ulceration, or ulcerative lesions, mostly involving the gastric corpus. The median overall survival time and survival time after diagnosis of metastatic cancer were 11 months [95% confidence interval (CI): 7–14] and 4.5 months (95% CI: 3–9), respectively. The survival analyses revealed that surgical interventions (including lung surgery and/or abdominal surgery) and systemic therapy (including chemotherapy, radiotherapy, and/or targeted therapy) seemed to be positive prognostic factors for both overall survival and survival after diagnosis of metastatic cancer.ConclusionsClinicians should be alerted to the occurrence of gastric metastasis in lung cancer patients. Comprehensive evaluation and appropriate treatment for specific patients may improve the survival rate of GMLC patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Gastric Metastasis of Primary Lung Cancer: Case Report and Systematic Review With Pooled Analysis

Tang

Liu

et al. 2022

Front. Oncol.

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“…Dacomitinib was approved by the FDA on September 27, 2018 for the treatment of NSCLC patients with EGFR del19 or exon 21 L858R mutations ( 73 ). However, second-generation EGFR-TKIs were not able to be administered at full strength to inhibit T790M mutant lung cancer due to adverse side effects, such as rash caused by inhibition of normal cells ( 23 ). Ding et al ( 74 ) concluded in a meta-analysis of clinical trials that afatinib resulted in a higher risk of rash than erlotinib or gefitinib.…”

Section: Egfr Inhibitors Used Clinicallymentioning

confidence: 99%

Mechanism of Lethal Skin Toxicities Induced by Epidermal Growth Factor Receptor Inhibitors and Related Treatment Strategies

Duan

et al. 2022

Front. Oncol.

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Epidermal growth factor receptor (EGFR) inhibitors are widely used to treat various types of cancers such as non-small cell lung cancer, head and neck cancer, breast cancer, pancreatic cancer. Adverse reactions such as skin toxicity, interstitial lung disease, hepatotoxicity, ocular toxicity, hypomagnesemia, stomatitis, and diarrhea may occur during treatment. Because the EGFR signaling pathway is important for maintaining normal physiological skin function. Adverse skin reactions occurred in up to 90% of cancer patients treated with EGFR inhibitors, including common skin toxicities (such as papulopustular exanthemas, paronychia, hair changes) and rare fatal skin toxicities (e.g., Stevens–Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis). This has led to the dose reduction or discontinuation of EGFR inhibitors in the treatment of cancer. Recently, progress has been made about research on the skin toxicity of EGFR inhibitors. Here, we summarize the mechanism of skin toxicity caused by EGFR inhibitors, measures to prevent severe fatal skin toxicity, and provide reference for medical staff how to give care and treatment after adverse skin reactions.

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“…The continuing improvements in the knowledge of the acquired EGFR-independent mechanisms of resistance to EGFR-TKIs, including oncogenic gene fusions, gene amplification, mutations affecting gene encoding for cell-cycle proteins, the activation of the epithelial-to-mesenchymal transition (EMT), as well as the NSCLC to SCLC histologic transformation, led to the investigation of the combination of additional targeted agents against identified secondary resistance to the previous EGFR-TKI, to bypass pathways or genetic aberrations [17]. The FLOWER observational multicenter study, performed on patients with EGFR-mutant advanced NSCLC receiving first-line osimertinib, investigated the type and pattern of disease progression with osimertinib.…”

Section: Continuing Egfr-tki Plus Other Targeted Agentsmentioning

confidence: 99%

Systemic Therapy for Oligoprogression in Patients with Metastatic NSCLC Harboring Activating EGFR Mutations

Rossi¹,

Galetta

2022

Cancers

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After a variable period of activity of the epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment, patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR mutations develop resistance to these TKIs. In some cases, an oligoprogression is diagnosed, and its management is still controversial. The oligoprogression represents an intermediate stage of metastatic NSCLC between localized and widely disseminated disease, and is characterized by a limited number and/or sites of metastases in which a disease progression appears, together with a more indolent tumor biology. Currently, the management of oligoprogressed NSCLC involves local treatment, including radiotherapy and/or surgery, to control the progressive lesions. Systemic therapy should also be a potential approach to boost the activity of EGFR-TKIs. However, considering the lack of large trials addressing this topic, the optimal therapeutic strategies remain undefined and should be evaluated on an individualized basis. In this paper, we review the most relevant scientific evidence of continuing the systemic therapy with the same EGFR-TKI for the management of patients with NSCLC harboring EGFR mutations and oligoprogressed to first-line EGFR-TKIs, also discussing the controversies and potential future directions.

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Hype or hope – Can combination therapies with third-generation EGFR-TKIs help overcome acquired resistance and improve outcomes in EGFR-mutant advanced/metastatic NSCLC?

Cited by 19 publications

References 234 publications

Gastric Metastasis of Primary Lung Cancer: Case Report and Systematic Review With Pooled Analysis

Gastric Metastasis of Primary Lung Cancer: Case Report and Systematic Review With Pooled Analysis

Mechanism of Lethal Skin Toxicities Induced by Epidermal Growth Factor Receptor Inhibitors and Related Treatment Strategies

Systemic Therapy for Oligoprogression in Patients with Metastatic NSCLC Harboring Activating EGFR Mutations

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