Abstract
Background MET exon 14 skipping mutation (METex14) is observed in ~3% of non-small cell lung cancer (NSCLC) cases and has been shown to be an independent poor prognostic factor associated with shorter overall disease-specific survival. Broad molecular testing can identify this biomarker in patients with advanced NSCLC (aNSCLC) and allow patients to be matched with the appropriate targeted therapy. This study examines biomarker testing patterns and clinical outcomes of chemotherapy and immuno-oncology (IO) monotherapy in aNSCLC patients with METex14.MethodsA descriptive retrospective study was conducted using the Flatiron Health–Foundation Medicine Inc. (FMI) clinico-genomic database. Patients with METex14 aNSCLC treated with systemic therapies were included in the biomarker testing analysis. The duration from specimen collection to reported results was assessed for PD-L1– and METex14-tested patients. Clinical outcomes were assessed in patients treated with chemotherapy or IO monotherapy. First-line (1L) and second-line (2L) real-world progression-free survival (rw-PFS) were estimated using Kaplan-Meier analysis.ResultsOf 91 METex14 patients eligible for the biomarker testing analysis, 77% and 60% received PD-L1 and FMI next-generation sequencing (NGS) testing within 3 months post aNSCLC diagnosis. Of those assessed for both PD-L1 and METex14 (n=9), the median duration between specimen collection and reporting was 1 week shorter for PD-L1 than for FMI NGS. Median 1L rw-PFS was 5.7 months (95% CI, 4.6-7.1) and 2.4 months (95% CI, 1.4-3.2) in patients receiving 1L chemotherapy (n=59) and IO monotherapy (n=18), with 3-month 1L rw-PFS rates of 78% and 33%. Median 2L rw-PFS was 3.5 months (95% CI, 1.9-11.1) and 4.7 months (95% CI, 2.8-12.9) in patients receiving 2L chemotherapy (n=16) and IO monotherapy (n=23), with 3-month 2L rw-PFS rates of 54% and 67%.ConclusionsThe median time from biopsy to test results appears 1 week shorter for PD-L1 than for FMI NGS. Chemotherapy and IO monotherapy were the most common regimens utilized but with limited PFS.
Highlights
Non-small cell lung cancer (NSCLC), which accounts for ~85% of lung cancer diagnoses, is a heterogeneous disease consisting of multiple histologies and many known driver mutations [1–4]
Patients who initiated chemotherapy or IO monotherapy as 1L or 2L were included in Real-world progression-free survival (rw-progression-free survival (PFS)) and overall survival (OS) analyses (Figure 1)
This study examined real-world testing patterns for PD-L1 and Foundation Medicine Inc (FMI) next-generation sequencing (NGS) testing and assessed the clinical outcomes with chemotherapy and IO monotherapy in patients with MET exon 14 skipping mutation (METex14) advanced NSCLC (aNSCLC) prior to capmatinib US approval
Summary
Non-small cell lung cancer (NSCLC), which accounts for ~85% of lung cancer diagnoses, is a heterogeneous disease consisting of multiple histologies and many known driver mutations [1–4]. In retrospective studies of patients with resected NSCLC, METex has been shown to be an independent poor prognostic factor and is associated with shorter overall survival [7, 8], underscoring the need for identification of this biomarker in patients with NSCLC and for targeted therapies [9]. A blinded independent review committee confirmed an overall response rate (ORR) of 68% (95% CI, 48%84%) and median duration of response (DOR) of 12.6 months (95% CI, 5.6 months-not estimable [NE]) among treatmentnaive patients (N=28). MET exon 14 skipping mutation (METex14) is observed in ~3% of nonsmall cell lung cancer (NSCLC) cases and has been shown to be an independent poor prognostic factor associated with shorter overall disease-specific survival. This study examines biomarker testing patterns and clinical outcomes of chemotherapy and immuno-oncology (IO) monotherapy in aNSCLC patients with METex
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