New Verse for a Familiar Song: Small Molecule Inhibitors for <i>MET exon 14</i> Skipping Non-Small Cell Lung Cancer

Le, Xiuning; Heymach, John V.

doi:10.1634/theoncologist.2020-0760

Cited by 9 publications

(7 citation statements)

References 29 publications

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“…Patients from the MET-amplification cohort however, were younger than the typical patient with NSCLC. Similar results were shown in a US retrospective analysis of 99 patients with lung adenocarcinoma, and MET amplification (mean MET ≥ 5), with a median age of 61 years at diagnosis; 66% were current or former smokers [12]. Similarly, in the MET-amplification cohort in the current study, most patients were either current or former smokers and had, on average, only recently stopped smoking.…”

Section: Orr Criteriasupporting

confidence: 88%

“…The common standard of care in first-line therapy for NSCLC, without oncogenic drivers, involves use of platinum-based chemotherapy or immune checkpoint inhibitors (ICIs) either as single components or in combination, depending on the level of expression of programmed death-ligand 1 (PD-L1) or potential contraindications such as poor performance status, often found in patients of advanced age [8][9][10][11][12]. For patients advancing to second-line therapy, monotherapy with ICIs should be considered, if not previously given.…”

Section: Introductionmentioning

confidence: 99%

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Real-world insights into patients with advanced NSCLC and MET alterations

Bittoni¹,

Yang²,

Shih³

et al. 2021

Lung Cancer

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To describe characteristics, treatment and outcomes of non-small cell lung cancer (NSCLC) patients with MET alterations (MET exon 14 [METex14] skipping or MET amplification [METamp]) in real-world clinical care. Methods: This non-interventional cohort study used real-world data extracted from electronic medical records from academic oncology sites in Israel, The Netherlands, Taiwan, and the USA. Patients had confirmed diagnosis of advanced (Stage IIIB-IV) NSCLC harboring MET alterations (date of diagnosis = index date) between 1 Jan 2010 and 30 Sept 2018. Medical history was assessed prior to and at the index date (baseline period), and outcomes from first date of treatment to death, loss to follow-up, or end of study period. Results: A total of 117 patients were included (METex14 n = 70; METamp n = 47); testing methods were heterogeneous. Concomitant oncogenic mutations were more common in the METamp cohort than METex14. Patients in the METex14 cohort were older than those in METamp, and a larger proportion were never smokers. Anticancer first-line therapies received by patients (METex14; METamp) included chemotherapy only (44%; 41%), MET inhibitors (33%; 29%), immune checkpoint inhibitor (ICI) mono-(12%; 15%) and combinationtherapy (8%; 3%). Second-line therapies included chemotherapy (35%; 30%) and MET inhibitors (30%; 39%). In the METex14 cohort, objective response rate (ORR) was generally low (first-line 28%; second-line 30%); no patients who received ICIs had a response. In the METamp cohort, ORR was 36% in first-line and 22% in secondline. Median (95% confidence interval) overall survival from start of first-line therapy was 12.0 months (6.8, 19.2) in the METex14 cohort and 22.0 months (9.8, 31.2) in METamp.

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Section: Orr Criteriasupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Real-world insights into patients with advanced NSCLC and MET alterations

Bittoni¹,

Yang²,

Shih³

et al. 2021

Lung Cancer

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“…As MET ex14 skipping often occurs in patients with NSCLC with older age ( 19 ), analysis was performed according to age. ORR by IRC in patients <75 years was 48.8% (95% CI: 37.7–60.0), and 39.7% (95% CI: 28.0–52.3) in patients ≥75 years ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Tepotinib Efficacy and Safety in Patients with MET Exon 14 Skipping NSCLC: Outcomes in Patient Subgroups from the VISION Study with Relevance for Clinical Practice

Sakai

Felip³

et al. 2022

Clinical Cancer Research

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Purpose: Primary analysis of VISION showed tepotinib had durable clinical activity in patients with MET exon 14 (METex14) skipping non–small cell lung cancer (NSCLC). We present updated outcomes for clinically relevant subgroups. Patients and Methods: This phase II, open-label, multi-cohort study of 500 mg (450 mg active moiety) tepotinib in patients with METex14 skipping NSCLC assessed efficacy and safety in predefined subgroups according to age, prior therapies (chemotherapy and immune checkpoint inhibitors), and brain metastases. An ad hoc retrospective analysis using Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria assessed intracranial activity. Results: 152 patients were evaluable for efficacy (median age: 73.1). Overall, objective response rate (ORR) was 44.7% [95% confidence interval (CI): 36.7–53.0]. Patients aged <75 (n = 84) and ≥75 (n = 68) had ORRs of 48.8% (95% CI: 37.7–60.0) and 39.7% (95% CI: 28.0–52.3), respectively. Treatment-naïve (n = 69) versus previously treated (n = 83) patients showed consistent efficacy [ORR (95% CI): 44.9% (32.9–57.4) vs. 44.6% (33.7–55.9); median duration of response (95% CI): 10.8 (6.9–not estimable) vs. 11.1 (9.5–18.5) months]. Of 15 patients analyzed by RANO-BM (12 received prior radiotherapy), 13 achieved intracranial disease control; 5 of 7 patients with measurable brain metastases had partial intracranial responses. Of 255 patients evaluable for safety, 64 (25.1%) experienced grade ≥3 treatment-related adverse events (TRAE), leading to discontinuation in 27 patients (10.6%). Rates of adverse events (AE) were broadly consistent irrespective of prior therapies. Conclusions: Tepotinib showed meaningful activity across subgroups by age, prior therapies, and brain metastases, with a manageable safety profile and few treatment discontinuations. See related commentary by Rosner and Spira, p. 1055

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“…This alteration can be detected by analysing circulating tumour DNA (ctDNA) in plasma obtained from liquid biopsy samples, or through analysing RNA/DNA from tissue biopsy samples. Compared to patient populations defined by other actionable alterations, patients with MET exon 14 skipping are typically older, more evenly distributed by sex, and have a greater proportion of current/former smokers ( 10 , 11 ) .…”

Section: Introductionmentioning

confidence: 99%

Tepotinib in patients with NSCLC harbouring MET exon 14 skipping: Japanese subset analysis from the Phase II VISION study

Morise

Kato

Matsumoto

et al. 2021

Japanese Journal of Clinical Oncology

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Background MET exon 14 skipping is an oncogenic driver occurring in 3–4% of non-small cell lung cancer (NSCLC). The MET inhibitor tepotinib has demonstrated clinical efficacy in patients with MET exon 14 skipping NSCLC. Here, we present data from Japanese patients in the Phase II VISION study, evaluating the efficacy and safety of tepotinib. Methods In the open-label, single-arm, Phase II VISION study, patients with advanced/metastatic NSCLC with MET exon 14 skipping received oral tepotinib 500 mg once daily. The primary endpoint was objective response by independent review. Subgroup analyses of Japanese patients were preplanned. Results As of 1 January 2020, 19 Japanese patients received tepotinib and were evaluated for safety, 15 of whom had ≥9 months’ follow-up and were also analysed for efficacy. By independent review, objective response rate (ORR) was 60.0% (95% confidence interval [CI]: 32.3, 83.7), median duration of response was not reached (95% CI: 6.9, not estimable [ne]), and progression-free survival was 11.0 months (95% CI: 1.4, ne). ORR in patients with MET exon 14 skipping identified by liquid biopsy (n = 8) was 87.5% (95% CI: 47.3, 99.7), and by tissue biopsy (n = 12) was 50.0% (95% CI: 21.1, 78.9). Patients’ quality of life was maintained with tepotinib treatment. Among patients evaluated for safety, the most common treatment-related adverse events (any grade) were blood creatinine increase and peripheral oedema (12 and nine patients, respectively). Conclusions Tepotinib demonstrated robust and durable clinical efficacy in Japanese patients with advanced NSCLC harbouring MET exon 14 skipping, identified by either liquid or tissue biopsy. The main adverse events, blood creatinine increase and peripheral oedema, were manageable.

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New Verse for a Familiar Song: Small Molecule Inhibitors for MET exon 14 Skipping Non-Small Cell Lung Cancer

Cited by 9 publications

References 29 publications

Real-world insights into patients with advanced NSCLC and MET alterations

Real-world insights into patients with advanced NSCLC and MET alterations

Tepotinib Efficacy and Safety in Patients with MET Exon 14 Skipping NSCLC: Outcomes in Patient Subgroups from the VISION Study with Relevance for Clinical Practice

Tepotinib in patients with NSCLC harbouring MET exon 14 skipping: Japanese subset analysis from the Phase II VISION study

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