Exploring Ways to Broaden the Reach of Molecular Tumor Testing

Thomas Zander, MD, far right, at the ASCO press conference where his community screening study was discussed. Also on the panel are, from left, George D. Demetri, MD, Caroline Robert, MD, PhD, Axel Hauschild, MD, and James Chih-Hsin Yang, MD, PhD.

The development of targeted therapies for a variety of tumor types has highlighted a greater need for widespread molecular testing to determine which patients have the mutations that these therapies target, and oncologists throughout the world are trying different approaches to translating such advances into broad clinical practice.

In Germany, the feasibility of a community screening program for patients with non-small cell lung cancer (NSCLC) was explored, a strategy that provoked discussion at this year’s annual ASCO meeting.

“High-quality molecular diagnostics and personalized treatment approaches present a significant benefit for patients,” said Thomas Zander, MD, of the University Hospital in Cologne, Germany, during a press conference at which his study was discussed.

“At last year’s ASCO meeting, [studies of] large networks for molecular screening testing were presented which consisted of several highly specialized comprehensive cancer centers spread all over the United States, but it meant that getting access to molecular diagnostics was only available to a minority of patients in this country,” Zander said.

Zander’s study focused on testing patients outside of large academic medical centers. In order to perform the study, researchers established the Network Genomic Medicine Lung Cancer. This network included community hospitals in the Cologne-Bonn region of the country, where approximately 2.5 million residents could potentially receive screening.

In all, 2032 samples from NSCLC patients were collected, the authors reported in their abstract. The figure includes 1782 samples from residents of the Cologne-Bonn region, which investigators estimate accounts for between 60% and 70% of all potential NSCLC samples in the area.

Of these samples, 77% were suitable for molecular testing. Samples of tumors of patients with lung adenocarcinoma—the most common form of NSCLC–were screened for ALK translocations, mutations in KRAS, EGFR, BRAF, and PIK3CA, and amplification of ERBB2. Squamous cell samples were screened for FGFR1 amplifications.

Forty percent of the samples carried mutations for which targeted therapies have been identified, aiding the community hospitals in providing treatment to these patients. For example, patients with ALK mutations were given crizotinib, and patients with EGFR mutations were given EGFR tyrosine kinase inhibitor treatment. Additionally, patients were also referred to clinical trials based on their genetic profiles that involved the testing of other targeted therapies in development.

NSCLC by Subtype and Mutation Frequency¹

77% of samples suitable for mutation analysis

NSCLC indicates non-small cell lung cancer, NOS, not otherwise specified.

Zander said the cost for the screenings ranged from approximately €500 to €1000 per patient. ($600 to $1200).

In the United States and elsewhere, different models are being used. Panel members commented from their vantage points.

“We’re doing a $35 million philanthropically funded trial where patients are allowed access to molecular diagnostics and information is fed back as clinically actionable, and they’re not charged for it,” said George D. Demetri, MD, director of the Center for Sarcoma and Bone Oncology at the Dana-Farber Cancer Institute in Boston, Massachusetts.

“We think that’s important because in the next five years we need that landscape to see what’s truly actionable, what’s truly important, and then we feel that we can commoditize the molecular testing,” said Demitri. “I think that’s what you’re seeing across the world.”

In France, the French National Cancer Institute has set up 28 laboratories in public hospitals to test for biomarkers, and all patients with cancer receive free testing for biomarkers such as KRAS, EGFR, and BRAF. However, these clinics are limited to proven biomarkers.

“In France, as soon as it is proven that a targeted agent is active against a disease, the mutation research is reinforced by the French social security system,” said Caroline Robert, MD, PhD, the head of Dermatology at the Institute Gustave Roussy in Paris, France. “The problem is for the mutations that are still in the discovery process, with the agents that are not yet on the market.”

Cost factors are important considerations in molecular screenings, and reimbursement practices vary.

“The problem is who should pay for this,” said James Chih-Hsin Yang, MD, PhD, a professor and director of Cancer Research at the National Taiwan University in Taipei. “In some of the countries, these mutational tests are paid for by insurance companies, such as in Japan. In some countries, these are non-reimbursable at this moment, but I think as more data are coming in, there [will be] no way to deny the reimbursement.”

Though no universal system of molecular testing or reimbursement exists, studies such as the one Zander presented at ASCO suggest that widespread screening is becoming an increasingly feasible and promising way of treating cancer patients.

“It proves that we can choose the most appropriate targeted therapy for patients, we can enroll patients in the appropriate targeted trials,” said moderator Sylvia Adams, MD, assistant professor in the Department of Medicine at New York University Langone Medical Center in New York City. “There is meaningful outcome when we select patients.”

Photo by © ASCO/Todd Buchanan 2012

Reference

1. Zander T, Heukamp LC, Bos MCA, et al. Regional screening network for characterization of the molecular epidemiology of non-small cell lung cancer (NSCLC) and implementation of personalized treatment. J Clin Oncol. 2012;30(suppl; abstr CRA10529).