Clearity’s Precision Medicine Symposium Demonstrates Sea Change in Personalized Ovarian Cancer Treatment

Precision Medicine

By: Cory Bentley, PhD

The Society for Gynecological Oncology (SGO) Meeting this March in San Diego brought together physicians and scientists from all over the world to share the latest research, treatments, and thinking in gynecological cancers including ovarian. Clearity co-hosted a symposium with Foundation Medicine, Inc entitled “Precision Medicine for Ovarian Cancer Care.”

Ovarian cancer care providers and advocates discussed the challenges and offered solutions for treating this genetically and molecularly variable disease. Ovarian cancer is so diverse that it is effectively many different diseases. Ovarian cancer therapies that have treated all patients the same have been catastrophic failures for many women. However, there are often not enough ovarian cancer patients with the matching molecular and genetic profile to the drug being tested to effectively run traditional clinical trials to prove the efficacy of the drug. The symposium speakers discussed the merits and opportunities to matching ovarian cancer patients with treatments designed to fit their molecular and genetic profiles.

Match Clinical Trials Show Promising Results

Symposium speaker Dr. Maurie Markman, from Cancer Treatment Centers of America, suggested that a trial design that does not require huge numbers of ovarian cancer patients may be a more practical way to evaluate new treatment options. He pointed to the success of several match trials. These trials enrolled patients with a variety of advanced recurrent cancers.

Patients were matched to a targeted treatment based on the genetic alterations in their tumors rather than their cancer type, such as ovarian or breast.

Targeted treatments are drugs that act on a specific biological pathway or molecule in the cancer cell. For example, if a patient has a mutation in the BRAF gene, she will receive a drug that inhibits the BRAF protein; the BRAF mutation is matched with a BRAF inhibitor. These trials test the effectiveness of a drug that blocks the presumed “active” molecular pathway in all cancer patients who have that specific molecular profile rather than focusing on the very limited number of ovarian cancer patients. Most reported match trials have demonstrated better response rates and outcomes for patients receiving matched treatment than those with unmatched treatments (e.g., https://www.ncbi.nlm.nih.gov/pubmed/20921468, https://www.ncbi.nlm.nih.gov/pubmed/24987059).

Some of the patients in the trials experienced remarkable responses, especially in consideration of the very difficult-to-treat patients enrolled in those trials. However, one recent trial saw virtually no difference between matched-drug treated and unmatched-drug treated patients and underscore the need for additional carefully designed clinical trials that also include options for drug combination therapy. These match trials expand the spectrum of anticancer drugs available to ovarian cancer patients and will help determine how to best match patients with drugs so that the number of patients who benefit is increased. This endeavor is part of the new frontier in ovarian cancer treatment.

Case Studies Highlight The Effectiveness Of Profile-Matched Drugs

Clearity patients are being matched right now using molecular and genetic profiling. Three speakers (Dr Premal Thaker of the Siteman Cancer Center, Dr. Kathleen Moore of the Stephenson Cancer Center, and Dr. Michael Castro of Personalized Cancer Medicine, PLLC in Honolulu) at the SGO symposium presented case studies of patients who were matched to treatments based on the DNA sequencing of their tumors. A case study is also described as an “n of one” study where n is the number of subjects tested. Each case study presented was an example of an ovarian cancer patient whose rare mutation was used to match her to a specific treatment. Dr. Castro presented a case study of his patient with an uncommon form of ovarian cancer—clear cell. Her tumor had progressed rapidly despite surgical removal, standard chemotherapy, and then chemotherapy for advanced disease. She was out of options and had shown little response to the rounds of chemotherapy. To potentially identify new options for her, her tumor was molecularly profiled with the assistance of the Clearity Foundation. A genetic analysis of her tumor by Foundation Medicine revealed a mutation in the KRAS gene, matching her to the anticancer drug Trametinib. On a treatment plan that included Trametinib, Dr. Castro’s patient saw a significant regression of tumors that had by this time metastasized to her lung and liver. Her near complete response to this drug lasted five months and she experienced no side effects from the treatment, a stark contrast from her prior treatments.

Dr. Castro describes Trametinib as the “right drug” for this patient. He published this case study with The Clearity Foundation in Gynecologic Oncology Research Practice. When asked if medicine can truly be advanced by case studies that involve a single subject, Dr. Castro responded, “Saying we don’t want case [studies] is against the spirit of medicine. One case study could change the world.” That his clear cell ovarian cancer patient responded to a matched therapy when everything else failed her is a powerful narrative in any context, scientifically and personally.

By telling the story of this woman and others like her, physicians let the rest of the medical community know about uncommon clinical situations where non-standard therapeutic approaches have been successful. Case studies alert other physicians as well as the entire patient and medical community to potential uses of drugs for cancers that have not already been approved. The success of matching individual patients to targeted treatments that are effective in both case studies and match clinical trials is driving ovarian cancer treatment to a personalized approach that gives patients more options and better outcomes.

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