Intrapatient comparisons of efficacy in a single-arm trial of entrectinib in tumour-agnostic indications

Krebs, Matthew; Blay, Jean‐Yves; Tourneau, C. Le; Hong, David S.; Véronèse, L.; Antoniou, Miranta; Bennett, Iain

doi:10.1016/j.esmoop.2021.100072

Cited by 14 publications

(10 citation statements)

References 20 publications

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“…In the subgroup of NSCLC, the ORR was 70% (7/10). Furthermore, intrapatient comparisons of entrectinib efficacy in the STARTRK-2 trial indicated that the ORR was higher and the median PFS was longer for entrectinib than discontinuation since the last therapy ( 83 ). Additionally, a case report showed that a patient with SQSTM1-NTRK1 fusion-positive advanced lung adenocarcinoma was treated with entrectinib, then developed partial response and had a complete remission of all brain metastases ( 41 ).…”

Section: Trk Inhibitors and Resistancementioning

confidence: 99%

NTRK Fusion in Non-Small Cell Lung Cancer: Diagnosis, Therapy, and TRK Inhibitor Resistance

et al. 2022

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Neurotrophic tropomyosin receptor kinase (NTRK) gene fusion has been identified as an oncogenic driver of various solid tumors, and it is rare in non-smalll cell lung cancer (NSCLC) with a frequency of approximately less than 1%. Next-generation sequencing (NGS) is of priority for detecting NTRK fusions, especially RNA-based NGS. Currently, the tropomyosin receptor kinase (TRK) inhibitors have shown promising efficacy and well tolerance in patients with NTRK fusion-positive solid tumors, regardless of tumor histology. The first-generation TRK inhibitors (larotrectinib and entrectinib) are recommended as the first-line treatment for locally advanced or metastatic NSCLC patients with positive NTRK fusion. However, TRK inhibitor resistance can eventually occur due to on-target or off-target mechanisms. Further studies are under investigation to overcome resistance and improve survival. Interestingly, NTRK fusion might be the mechanism of resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI) in NSCLC patients with EGFR mutation. Regarding immunotherapy, the efficacy of immune checkpoint inhibitors in NSCLC patients harboring NTRK fusion has yet to be well described. In this review, we elucidate the function of NTRK genes, summarize the diagnostic techniques for NTRK fusions, and present clinical data for TRK inhibitors; we also discuss potential mechanisms of resistance to TRK inhibitors.

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Section: Trk Inhibitors and Resistancementioning

confidence: 99%

NTRK Fusion in Non-Small Cell Lung Cancer: Diagnosis, Therapy, and TRK Inhibitor Resistance

et al. 2022

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“…The Krebs et al (2021) intra-patient comparison did not include an evaluation of any safety end points. 90…”

Section: Harmsmentioning

confidence: 99%

Entrectinib (Rozlytrek)

CADTH¹

2023

cjht

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CADTH reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class. The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada's federal, provincial, and territorial governments, with the exception of Quebec. This review assesses Entrectinib (Rozlytrek) capsules, 100 mg and 200 mg, oral. Indication: For the treatment of adult patients who have unresectable, locally advanced or metastatic extracranial solid tumours (including brain metastases), that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion without a known acquired resistance mutation and no satisfactory treatment options.

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“…In 2018 and 2019, the tropomyosin receptor kinase inhibitors larotrectinib and entrectinib were approved for patients with solid tumors harboring neurotrophic receptor tyrosine kinase ( NTRK ) gene fusions [4, 9, 10]. Subsequently, four more drugs have been approved, of which selpercatinib is the most recent, which is a multikinase inhibitor that inhibits wild-type RET and multiple mutated RET isoforms.…”

Section: Fda-approved Tissue-agnostic Drugsmentioning

confidence: 99%

The Potential of Trastuzumab Deruxtecan as a Tissue Agnostic Drug

Jørgensen

2023

Oncology

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Background: Many modern anticancer drugs are designed to target specific molecular alterations harbored by the cancer. If a specific drug is able to target these alterations, regardless of the organ or tissue in which the cancer originates, it will often be characterized as a tissue- or tumor agnostic drug. According to the Food and Drug Administration (FDA), a tissue-agnostic drug refers to a drug that targets a specific molecular alteration across multiple cancer types, as defined by organ, tissue, or tumor type. Summary: Over the last 6 years, the FDA has approved seven tissue-agnostic drugs, and more are anticipated in the future. One promising candidate for a tissue-agnostic classification is the antibody-drug conjugate trastuzumab deruxtecan (T-DXd). Currently, T-DXd is approved for the treatment of human epidermal growth factor receptor 2 (HER2)-positive and HER2-low breast cancer, HER2-positive gastric or gastroesophageal junction adenocarcinoma, and non-small cell lung cancer with activating HER2 mutations. Ongoing clinical research is exploring the potential of T-DXd in various solid tumors that harbor specific HER2 molecular alterations, and encouraging results, including the interim data from the DESTINY-PanTumor02 trial, have been published, which suggest a tissue-agnostic potential. Key Messages: Published phase I data as well as the interim results from the phase II DESTINY-PanTumor02 trial indicates that patients with different HER2-positive advanced solid tumors may benefit from treatment with T-DXd. Based on the currently available data, it seems likely that T-DXd possesses pantumor activity. However, different clinical trials are ongoing, and it will be necessary to see the results from these trials before drawing a final conclusion. When discussing tissue-agnostic potential, it is important to add that for most of the patients enrolled in the DESTINY-PanTumor02 and other trials, few treatment alternatives seem to exist, and T-DXd might be able to cover an unmet medical need.

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Intrapatient comparisons of efficacy in a single-arm trial of entrectinib in tumour-agnostic indications

Cited by 14 publications

References 20 publications

NTRK Fusion in Non-Small Cell Lung Cancer: Diagnosis, Therapy, and TRK Inhibitor Resistance

NTRK Fusion in Non-Small Cell Lung Cancer: Diagnosis, Therapy, and TRK Inhibitor Resistance

Entrectinib (Rozlytrek)

The Potential of Trastuzumab Deruxtecan as a Tissue Agnostic Drug

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