September 25, 2022

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Brain metastases from breast cancer: Small molecule TKI vs macromolecule monoclonal antibody

Brain metastases from breast cancer: Small molecule TKI vs macromolecule monoclonal antibody



 

Brain metastases from breast cancer: Small molecule TKI vs macromolecule monoclonal antibody.

For the treatment of brain metastases from breast cancer, which is stronger small molecule TKI vs macromolecule monoclonal antibody?

Positive results from clinical trial of Tislelizumab in first-line treatment of gastric. 

 

 

THE LANCET ONCOLOGY: Pyrotinib combined with capecitabine in the treatment of HER2-positive breast cancer with brain metastases

Patients with HER2-positive metastatic breast cancer are at high risk of developing brain metastases and lack effective treatment options.

Recently, a study investigating the activity and safety of pyrotinib combined with capecitabine in patients with HER2-positive metastatic breast cancer and brain metastases was published in THE LANCET ONCOLOGY. The treatment of HER2-positive breast cancer brain metastases has considerable clinical activity and safety.

 

Brain metastases from breast cancer: Small molecule TKI vs macromolecule monoclonal antibody

 

We conducted a multicenter, single-arm, two-cohort phase II trial in eight tertiary hospitals in China. Group A was naive HER2-positive brain metastases, and group B was patients with disease progression after radiotherapy. They received

pyrotinib 400 mg orally once a day and capecitabine 1000 mg/m 2 orally, twice a day, for 14 days days, followed by 7 days off every 3 weeks until disease progression or intolerable adverse effects.

The primary endpoint was investigator-confirmed intracranial objective response rate according to the Solid Tumor Response Evaluation Criteria (version 1.1).

 

A total of 78 women were recruited between January 29, 2019, and July 10, 2020. The intracranial objective response rate was 74.6% (95% CI: 61.6–85.0) in Group A and 42.1% (95% CI: 20.3–66.5) in Group B.

The most common sudden adverse reaction of grade 3 or higher was diarrhea (24% in arm A and 21% in cohort B). Two (3%) patients in Arm A and three (16%) patients in Arm B had treatment-related serious adverse events.

 

This is the first prospective study to show the activity and safety of pyrotinib in combination with capecitabine in patients with HER2-positive breast cancer and brain metastases, especially in radiotherapy-naïve populations, and warrants a randomized controlled trial for further verification.

 

 

 

Cancer Cell: MEK inhibitors may enhance the synergistic effect of immune and chemotherapy

Combination chemotherapy with PD-1/PD-L1 inhibitors has become the standard treatment for patients with metastatic non-small cell lung cancer (mNSCLC), however, pemetrexed and cisplatin (PEM/CDDP) chemotherapy cannot be combined with immune checkpoint inhibitors (ICIs). ) produce a synergistic effect.

Recently, a study investigating MEK inhibitors to overcome chemoimmunotherapy resistance by inducing CXCL10 in cancer cells was published in Cancer Cell.

The results showed that MEK inhibitors and chemotherapy combined with PD-L1 blockade. Synergistic effect.

 

Brain metastases from breast cancer: Small molecule TKI vs macromolecule monoclonal antibody

 

We linked the failure of PEM/CDDP chemotherapy to synergize with ICIs in a lung tumor model and its failure to induce CXCL10 expression and CD8 T cell recruitment.

Using drug screening, we found that combining a MEK inhibitor (MEKi) with PEM/CDDP triggers CXCL10 secretion and CD8 T cell recruitment in tumor cells, sensitizing them to ICIs.

PEM/CDDP combined with MEKi promotes optic nerve protein (OPTN)-dependent mitophagy to produce CXCL10 in a mitochondrial DNA and TLR9-dependent manner.

TLR9 or autophagy/mitochondrial inhibition abolished the antitumor efficacy of PEM/CDDP combined with MEKi/anti-PD-L1 therapy.

Our findings underscore the role of TLR9 and OPTN-dependent mitophagy in enhancing the efficacy of chemoimmunotherapy.

 

 

references:
[1] Meric-Bernstam F, et al. Futibatinib, an Irreversible FGFR1-4 Inhibitor, in Patients with Advanced Solid Tumors Harboring FGF/FGFR Aberrations: A Phase I Dose-Expansion Study [published online ahead of print, 2021 Sep 22] .Cancer Discov.2021;10.1158/2159-8290.CD-21-0697.doi:10.1158/2159-8290.CD-21-0697 https://cancerdiscovery.aacrjournals.org/content/early/2022/01/19 /2159-8290.CD-21-0697

[2] Limagne E, et al. MEK inhibition overcomes chemoimmunotherapy resistance by inducing CXCL10 in cancer cells [published online ahead of print, 2022 Jan 17]. Cancer Cell. 2022;S1535-6108(21)00662-0.doi:10.1016 /j.ccell.2021.12.009 https://www.cell.com/cancer-cell/fulltext/S1535-6108(21)00662-0

 

(source:internet, reference only)


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