Use of erlotinib and thalidomide in advanced NSCLC patients with acquired resistance to erlotinib: A pilot study

Wang, Genhe; Wu, Pengfei; Zhang, Long-Hui; Fang, Ping; Chen, Yong; Zuo, Gang; Wu, Yiqing; Wang, Shuhong; Sun, Guoping

doi:10.1016/j.prp.2017.10.016

Cited by 4 publications

(2 citation statements)

References 18 publications

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“…After treatment with erlotinib plus thalidomide in 52 NSCLC patients with resistance to erlotinib, the ORR and DCR were 7.7% and 38.5%, respectively. Further preclinical/clinical studies are required to provide more information for guiding personalized therapy [ 81 ]. However, these combination treatments always produced serious adverse effects, especially in the case of bevacizumab and erlotinib, which caused the most adverse events of grade 3 or higher.…”

Section: Acquired Resistance and Corresponding Strategiesmentioning

confidence: 99%

Current Strategies for Treating NSCLC: From Biological Mechanisms to Clinical Treatment

Kwok

2020

Cancers

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The identification of specific epidermal growth factor receptor (EGFR)-activating mutations heralded a breakthrough in non-small-cell lung cancer (NSCLC) treatments, with the subsequent development of EGFR-tyrosine kinase inhibitor (TKIs) becoming the first-line therapy for patients harboring EGFR mutations. However, acquired resistance to EGFR-TKIs inevitably occurs in patients following initial TKI treatment, leading to disease progression. Various mechanisms are behind the acquired resistance, and mainly include (1) target gene modification, (2) alternative parallel pathway activation, (3) downstream pathway activation, and (4) histological/phenotypic transformation. Approaches to combat the acquired resistance have been investigated according to these mechanisms. Newer generations of TKIs have been developed to target the secondary/tertiary EGFR mutations in patients with acquired resistance. In addition, combination therapies have been developed as another promising strategy to overcome acquired resistance through the activation of other signaling pathways. Thus, in this review, we summarize the mechanisms for acquired resistance and focus on the potential corresponding therapeutic strategies for acquired resistance.

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Section: Acquired Resistance and Corresponding Strategiesmentioning

confidence: 99%

Current Strategies for Treating NSCLC: From Biological Mechanisms to Clinical Treatment

Kwok

2020

Cancers

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“…For solid cancers, the clinical activity of thalidomide monotherapy is limited [21], but recent in vitro studies demonstrated the synergistic effects of thalidomide in combination with TKIs on NSCLC [22,23]. A pilot study of thalidomide plus erlotinib in 52 advanced NSCLC patients with acquired resistance to erlotinib indicated the reversion effect of thalidomide on TKIacquired resistance [24]. In addition to the antiangiogenic and immunomodulatory actions, the characteristic of thalidomide as a molecular glue may contribute to the synergistic effect in solid cancers.…”

Section: Introductionmentioning

confidence: 99%

Pyrotinib combined with thalidomide in advanced non-small-cell lung cancer patients harboring HER2 exon 20 insertions (PRIDE): protocol of an open-label, single-arm phase II trial

Song

Hong

et al. 2021

BMC Cancer

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Background Standard therapy for human epidermal growth factor receptor 2 (HER2)-mutant non-small-cell lung cancer (NSCLC) is lacking. The clinical benefits with pan-HER inhibitors (afatinib, neratinib, and dacomitinib), anti-HER2 antibody drug conjugate (ADC) trastuzumab emtansine, and an emerging irreversible tyrosine kinase inhibitor (TKI) poziotinib were modest. Another new ADC trastuzumab deruxtecan showed encouraging outcomes, but only phase I study was completed. Pyrotinib, another emerging irreversible epidermal growth factor receptor (EGFR)/HER2 dual TKI, has been approved in HER2-positive breast cancer in 2018 in China. It has shown promising antitumor activity against HER2-mutant NSCLC in phase II trials, but pyrotinib-related diarrhea remains an issue. The antiangiogenic and immunomodulatory drug thalidomide is a cereblon-based molecular glue that can induce the degradation of the IKAROS family transcription factors IKZF1 and IKZF3. The use of thalidomide can also decrease gastrointestinal toxicity induced by anti-cancer therapy. Methods This is an open-label, single-arm phase II trial. A total of 39 advanced NSCLC patients with HER2 exon 20 insertions and ≤ 2 lines of prior chemotherapy will be recruited, including treatment-naïve patients who refuse chemotherapy. Patients are allowed to have prior therapy with immune checkpoint inhibitors and/or antiangiogenic agents. Those who have prior HER2-targeting therapy or other gene alterations with available targeted drugs are excluded. Eligible patients will receive oral pyrotinib 400 mg once daily and oral thalidomide 200 mg once daily until disease progression or intolerable toxicity. The primary endpoint is objective response rate. Discussion The addition of thalidomide to pyrotinib is expected to increase the clinical benefit in advanced NSCLC patients with HER2 exon 20 insertions, and reduce the incidence of pyrotinib-related diarrhea. We believe thalidomide is the stone that can hit two birds. Trial registration ClinicalTrials.gov Identifier: NCT04382300. Registered on May 11, 2020.

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Effects of microRNA regulation on antiangiogenic therapy resistance in non-small cell lung cancer

Hui

Jiang

2020

Biomedicine & Pharmacotherapy

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Use of erlotinib and thalidomide in advanced NSCLC patients with acquired resistance to erlotinib: A pilot study

Cited by 4 publications

References 18 publications

Current Strategies for Treating NSCLC: From Biological Mechanisms to Clinical Treatment

Current Strategies for Treating NSCLC: From Biological Mechanisms to Clinical Treatment

Pyrotinib combined with thalidomide in advanced non-small-cell lung cancer patients harboring HER2 exon 20 insertions (PRIDE): protocol of an open-label, single-arm phase II trial

Effects of microRNA regulation on antiangiogenic therapy resistance in non-small cell lung cancer

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