Three Studies of Lung Cancer Patients with METex14 Skipping Mutation Presented at ASCO

Positive findings for Tepmetko and Tabrecta reported at ASCO.

A growing number of cancer treatments are designed to bypass other cells and home in only on those with alterations that spur on the rampant cell division that characterizes cancer. The alphabet soup of genetic targets includes the EGFR, ALK, and ROS1.

Another one of these targets are mesenchymal-epithelial transition (MET) exon 14 skipping alterations, which occur in approximately 3%-4% of patients with nonsmall cell lung cancer (NSCLC), often without accompanying other mutations that drive cancerous growth.

Researchers presented three abstracts concerning MET exon 14 (often abbreviated to METext14) skipping mutations and the drugs that target them at the annual meeting of the American Society of Clinical Oncology (ASCO) earlier this month.

Tepmetko passes cost muster

Using Tepmetko (tepotinib) in adult patients with metastatic NSCLC METex14 skipping mutations is expected to have minimal financial impact on Medicare and commercial payers in the United States, according to one abstract presented at meeting by researchers at EMD Serono, the biopharmaceutical subsidiary of Merck KGaA that markets the drug, and Evidera, a subsidiary of Pharmaceutical Product Development,a contract research organization. The FDA approved Tepmetko in February.

Investigators developed an economic model to project financial outlays from 2021 to 2023 for treatment regimens with or without Tepmetko. In hypothetical Medicare and commercial plans with one million members each, an estimated 160 Medicare patients and 32 adult patients from commercial plans with metastatic NSCLC would test positive for METex14 skipping mutations.

Of these, 26 Medicare and five commercial plan members would receive Tepmetko. In this hypothetical analysis, introducing Tepmetko reduced cumulative financial outlays by $661,379 and $151,700 for Medicare and commercial payers, respectively, primarily due to lower overall drug acquisition and disease management costs. Results are most sensitive to the clinical efficacy of tepotinib and Tabrecta (capmatinib).

The number of patients eligible for treatment with a tyrosine kinase inhibitor (TKI) was estimated from epidemiological data, real-world evidence, and forecasted biomarker testing rates. Investigators assumed this population has access to other TKI therapies such as Tabrecta and Xalkori (crizotinib). Resource utilization and 2020 costs were informed by online pricing databases, CMS fee schedules, Healthcare Cost and Utilization Project and trial data, expert opinion, and publicly available sources.

Positive patient-reported outcomes for Tabrecta

Tabrecta (capmatinib) was associated with clinically meaningful improvements in cough, delayed time to lung symptom, and preserved quality of life in patients with METex14 skipping mutated NSCLC, according to another abstract presented at the meeting. The FDA gave Tabrecta accelerated approval in May 2020.

This abstract presented patient-reported outcomes from the GEOMETRY mono-1 trial, a trial sponsored by Novartis, which markets Tabrecta. A total of 27 of 28 previously untreated patients and 65 of 69 pretreated patients completed patient-reported outcomes questionnaires at baseline and every six weeks until end of treatment.

Quality of life improved at all cycles in patients achieving clinical complete response or partial response with treatment with Tabrecta, while symptom worsening was seen in those with no clinical response. The researchers concluded that patient-reported outcomes support the use of Tabrecta in these patients.

Sequencing treatment choices: Checkpoint inhibitors, then TKIs

A third abstract looked at one center’s experience with the order of TKIs and immune checkpoint inhibitor (ICI) regimens in patients with METex14 skipping mutated NSCLC. Investigators with Princess Margaret Cancer Center in Toronto sought to characterize treatment patterns and outcomes in this patient population.

Investigators identified 43 patients with METalterations, of whom 29 had METex14 skipping alterations, Patients who were initially treated with checkpoint inhibitors had significantly longer overall survival.

Investigators found that patients with MET ex14 NSCLC benefit from checkpoint inhibitors regardless of PD-L1 expression or smoking history. Overall response rate and progression-free survival with earlier generation TKIs, such as Xalkori (crizotinib), were poor. However, Increased toxicity is seen when a TKI is used after checkpoint inhibitors.