Advertisement

ECC 2013: Molecular Sequencing Identifies Drug Targets for Cancers of Unknown Primary Origin

Advertisement

Key Points

  • Molecular profiling identified targetable, druggable abnormalities in 80% of patients with cancer of unknown primary origin, which occur in about 10% of all cancer patients.
  • Most of the targetable abnormalities identified in this study can be treated with conventional chemotherapy, not biologics.
  • Treatment outcomes are not currently available for most of the patients in this series, but success has been reported in a few patients.

Cancers of unknown primary origin pose a treatment dilemma for oncologists and a great deal of anxiety for patients and their families. A study reported at the European Cancer Congress 2013 in Amsterdam (Abstract LBA39) shows that molecular profiling can identify targetable mutations in up to 80% of patients with cancers of unknown primary origin. This is the largest study to date reported on this patient population.

“Molecular understanding and companion diagnostics have led to a paradigm shift in the treatment of solid tumors. This technology allows us to identify disease-causing mechanisms for cancers of unknown primary origin. We were pleasantly surprised to find that we could identify targetable mutations in up to 80% of cases, and some of these abnormalities can be targeted with older chemotherapies,” said lead author Zoran Gatalica, MD, DSc, Director of Oncologic Pathology at Caris Life Sciences in Phoenix.

Dr. Gatalica emphasized that conventional chemotherapies could be used for many of the cases of cancers of unknown primary origin. “Established protocols work. These older drugs are less expensive than targeted therapies, and are not drugs you normally think of as targeted therapy. Only a sliver of cases had abnormalities targetable by biologic therapies,” he commented.

Study Details

Dr. Gatalica and colleagues reviewed molecular profiling data on 1,400 cancers of unknown primary origin obtained from Caris Life Sciences, a referral laboratory. They looked at sequencing and matched biomarkers with clinical evidence in the literature on drugs that are effective in cancers with those biomarkers. Multiple methods of biomarker assessment were employed, including mutational analysis, in situ hybridization, immunohistochemistry, real-time polymerase chain reaction, and fragment analysis.

In the past, attempts were made to define the diagnosis of cancer of unknown primary origin by finding the primary site, but the tissue of the primary cancer and histologic subtype are insufficient to identify targets in metastatic sites, he told listeners.

“We need to go straight to the jugular to find what is driving these cancers,” he stated.

In this series of patients, cancer of unknown primary origin occurred more frequently in women than in men, and the average age of patients was 61 years; very few were under 20 years old, he said.

Personalized Medicine Can Be Conventional Chemotherapy

Dr. Gatalica noted that the profiling tests are reimbursable in the United States, even for repeated tests, and also noted that the cost of molecular testing is going down. He and his colleagues are encouraging oncologists to send in reports on the patients in this series to provide data on treatment of these abnormalities and outcomes.

“This is an extremely important paper. About 10% of all cancer patients have cancer of unknown primary origin, even after extensive workups. It is difficult to tell them and there families that we have no idea what the primary cancer is. The paper represents the largest group of patients with cancer of unknown primary origin ever to be reported.

“I think identifying these tumors with molecular profiling is the wave of the future,” stated Cora Sternberg, MD, moderator of the press conference where Dr. Gatalica discussed his findings.

“An important message for readers is that personalized medicine can be chemotherapy in many cases of cancer of unknown primary origin,” she emphasized.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


Advertisement

Advertisement



Advertisement