Clinical trials, health information technology platform to test power of precision medicine
CHICAGO — Precision medicine represents a potentially practice-changing advance in the landscape of cancer treatment.
Yet, the ability to gather and analyze data from each person with cancer to better inform future treatment approaches for the larger patient population remains a formidable challenge.
Two forthcoming clinical trials, including the first trial sponsored by ASCO, are designed to help match patients with advanced cancers to the best possible therapies based on the genetic makeup of their disease.
Further, implementation of the CancerLinQ data analytics platform — a health information technology platform designed to expand and improve patient-specific cancer care — can help analyze and disperse information gleaned from these trials and others.
Clifford A. Hudis
“These advances represent our ever-deepening understanding of cancer’s biology,” Clifford A. Hudis, MD, FACP, chief of the breast medicine service at Memorial Sloan Kettering Cancer Center and past president of ASCO, said during a press conference. “In turn, these advances are made possible by historic investment in cancer biology and science at the national level over many decades. … We have to find new ways of efficiently testing drugs according to the molecular characteristics of tumors. Simply put, this means testing drugs based upon the biology of cancer, not its anatomic source.”
The goal of the Targeted Agent and Profiling Utilization Registry (TAPUR) Study — ASCO’s first clinical trial — is to gather information related to the real-world practice of precision medicine in patients with cancer.
“Increasingly, we find that patients with advanced cancers no longer have any standard treatment options,” Richard L. Schilsky, MD, FACP, FASCO, chief medical officer of ASCO, said during a press conference. “Now that genomic profiling is readily available throughout the clinical oncology community, sometimes a potentially actionable variant is detected … and that leads to the consideration [that] treating a patient with a certain drug might be beneficial.”
Researchers involved with the TAPUR trial will analyze the anti-tumor activity and toxicity of commercially available anti-cancer drugs in patients whose tumors harbor a targetable genomic variant. The trial is designed to facilitate patient access to potentially efficacious, targeted anti-cancer therapies.
The trial will include patients with advanced solid tumors, B-cell non-Hodgkin’s lymphoma and multiple myeloma for whom no standard treatment options exist.
“In some cases, the drugs used will be investigational drugs, and the patients will be treated in a conventional clinical trial,” Schilsky said. “In other cases, given the large number of targeted therapies commercially available, the best option may be to receive a commercially available targeted drug prescribed outside of the FDA-approved mutation.”
TAPUR researchers intend to begin enrolling patients later this year. At press time, five drug companies — AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Genentech and Pfizer — agreed to provide a combined 13 therapeutic agents. ASCO will conduct the study in association with The Netherlands Cancer Center for Personalized Cancer Treatment.
“We decided to join forces and essentially do an identical protocol in both countries,” Schilsky said.
The NCI-Molecular Analysis for Therapy Choice (MATCH) trial also is designed to evaluate data from precision medicine approaches in cancer treatment.
“[NCI-MATCH] is a foundational discovery trial, where we will try to understand how molecular abnormalities affect the response to targeted therapies, rather than the histology of origin,” James H. Doroshow, MD, director of the division of cancer treatment and diagnosis at the NCI, said during a press conference. “It uses an integrated and validated diagnostic to refine patient care and refine our understanding of how we are going to move forward [with precision medicine].”
Researchers involved with the NCI-MATCH trial will use genomic profiling to assign patients — regardless of tumor type — to targeted therapies based on the molecular abnormalities of their tumors. Researchers also seek to determine which targeted therapies do not benefit patients with certain mutations.
“There are very rare instances of a cancer gene that sits within just one cancer type,” Keith T. Flaherty, MD, associate professor at Harvard Medical School and an investigator on the NCI-MATCH trial, said during a press conference. “We need to hone in on an understanding of the relevant genetic makeup and building blocks within cancer types and across cancer types.”
Barbara A. Conley
The researchers plan to launch the trial in July with 10 study arms from the National Cancer Treatment Network. The trial will include patients from academic and community centers in urban and rural areas.
An additional 12 arms will join the study in a rolling fashion, according to Barbara A. Conley, MD, associate director of the cancer diagnosis program at the NCI.
“It has been a highly coordinated effort,” Conley said. “One of the key things we tried to do was to go where the expertise is, get that expertise and employ it in this trial.”
The initial 10 arms will evaluate approved targeted treatments, including crizotinib (Xalkori, Pfizer) for ALK rearrangement and ROS1 translocation, dabrafenib (Tafinlar, Novartis) and trametinib (Mekinist, Novartis) for BRAF V600E or V600K mutations, and trametinib monotherapy for BRAF fusions or non-V600E/V600K mutations. Investigators also will evaluate investigational targeted agents, such as afatinib (Gilotrif, Boehringer Ingelheim) for epidermal growth factor receptor activating mutations and HER-2 activating mutations, sunitinib (Sutent, Pfizer) for c-KIT mutations, and ado-trastuzumab emtansine (Kadcyla, Genentech) for HER-2 amplification.
Study protocol calls for 3,000 patients to undergo initial screening, with the intention to identify and enroll 1,000 patients.
“It is essential that the eligibility assays accurately identify patients with the appropriate molecular features in their tumors,” Conley said. “It is just as important that we do not identify patients as having a mutation if they do not.”
ASCO began developing the CancerLinQ health information technology platform in 2010 and presented the first demonstration of the software at the 2015 ASCO Annual Meeting.
CancerLinQ is designed to securely make available real-world patient care data from electronic health records and allow physicians to use the information to consider potential treatment options.
“This platform [was developed] by physicians, for physicians,” Allen S. Lichter, MD, FASCO, CEO of ASCO, said during a press conference. “We are not only providing the platform to our colleagues, but we will be asking for their input for its improvement.”
CancerLinQ (SAP) will be available in late 2015. The initial rollout will include 15 hospitals around the United States and contain data from approximately 500,000 patients.
Lichter identified several areas in which CancerLinQ holds the potential to dynamically change oncology practice, including the ability for clinicians to access electronic records in a streamlined, updated manner.
“Doctors will be able to see, in an instant, information related to patients’ characteristics, the kind of care they received and the outcomes they have experienced,” he said. “They will see a longitudinal record of any patient’s case. I believe physicians will [come to] say, ‘I cannot practice without it.’”
Previous software acted as “the electronic equivalent of a paper chart,” Lichter said, whereas the new approach has the potential for optimal efficiency.
The ability for physicians to assess quality of care is another potential reward of CancerLinQ, Lichter said.
“At its heart, CancerLinQ is a quality-of-care program,” he said. “The big difference between this quality-of-care program and past programs is that most quality programs are, to some extent, tests. You look retrospectively, you get a report card. … What we are trying to do is to error-proof the system.”
CancerLinQ will enable physicians to compare their performance with the performance of their peers, both within their own practice and within the entire CancerLinQ network.
“There is nothing more powerful in improving physician quality than to simply measure it and display it,” Lichter said.
The 15 practices scheduled to participate in the CancerLinQ rollout range in size from a six-person community practice to NCI comprehensive cancer centers, Lichter said.
“We know the experiences of these trailblazing practices will allow us to create the experience we need to make CancerLinQ a reality,” he said. – by Cameron Kelsall
Disclosure: CancerLinQ is a wholly-owned nonprofit subsidiary of ASCO and was developed using SAP HANA. Hudis, Lichter and Schilsky report leadership roles with ASCO. Flaherty reports consultant roles with and stock ownership in Amgen, Compugen, Flexus Biosciences, Genentech/Roche, GlaxoSmithKline, Kite Pharma, Merck and Novartis.