Clinical Trials for Ovarian Cancer Patients: Why Now?

Clinical Trials for Ovarian Cancer Patients: Why Now?

The Clearity Foundation

Dr. Cory Bentley, PhD and Dr. Teresa Gallagher, PhD

Ovarian cancer is a very diverse disease on the molecular level. Different tumors have different key molecular players and potentially different Achilles’ heels. Researchers are making real progress in pinpointing key players involved in this disease, spurring the movement of new drugs into the clinic that target these newly identified players.  For example, a 2011 study by The Cancer Genome Atlas (TCGA) research consortium found that ~35% of ovarian cancers have alterations in a molecular pathway known as PI3K/AKT. This pathway is important in cancer cell growth. New drugs targeting this pathway have entered clinic trials for ovarian cancer patients (e.g. MK-2206, which targets AKT and BYL719, which targets PI3K).

“This is cutting edge science,” says Dr. Evan Friend, who volunteers with Clearity to evaluate clinical trial data. Dr. Friend points out that if an ovarian cancer patient’s tumor suggests that her cancer may be responsive to a clinical trial drug, it gives her more treatment options that may lead to remission. “Although these drugs are new, there is a foundation of research supporting their clinical evaluation.” Drugs that progress into clinical trials have already been thoroughly evaluated and tested in the laboratory and in animal models. By considering clinical trial drugs in addition to already approved drugs, more opportunities open for ovarian cancer patients to tailor their treatments to match their molecular profiles. This approach of matching treatment options to the patient’s molecular profile defines personalized medicine.

Continuing progress in understanding molecular drivers in cancer, combined with significant technological advances in evaluating the associated molecular profiles, provide new opportunities for ovarian cancer patients to personalize their treatments. Foundation Medicine is leveraging these cutting edge advancements, so-called next-generation sequencing, to perform genomic analysis to detect alterations in relevant cancer genes. While Clearity’s standard profile is focused on markers relevant to approved drugs, the genomic information that is obtained by sequencing a more expansive set of genes may have implications for drugs in clinical trials. Ovarian cancer molecular profiling from both panels provides the most comprehensive molecular profile available for ovarian cancer patients to date. The  best-tailored fit may be from already approved drugs or may be from drugs just now making their way through clinical trials or from a combination chemotherapy-clinical trial drug based on the individual tumor profile.

There are currently 235 ongoing clinical trials for ovarian cancer in the United States. Approximately 25% of these are testing drugs that target specific proteins and pathways that have been shown to be active in pre-clinical ovarian cancer models.  More drugs will continue to enter clinical trials, increasing the opportunities and options for ovarian cancer patients.

The information included in this newsletter is for educational purposes only. It is not intended nor implied that this information be a substitute for professional medical advice. You should always consult your healthcare provider to determine the appropriateness of the information for your own situation.

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Towards Individualised Treatment in Ovarian Cancer

Results of recent studies have greatly changed our understanding of ovarian carcinogenesis. The time-honoured notion that ovarian cancer originates from epithelium on the surface of the ovaries that invaginates into the underlying stroma, undergoes malignant transformation, and then spreads from the ovary to distant pelvic and intra-abdominal sites has been abandoned. Instead, a dualistic model was proposed for a group of rather indolent and genetically stable tumours (type I) and a large group of highly aggressive and genetically unstable tumours (type II). Type I tumours often are diagnosed in early stage, confined to the ovary, and develop from precursors such as borderline ovarian tumours, whereas type II cancers present at an advanced stage and originate from a putative precursor lesion in the fallopian tube. On the molecular level, type II tumours are characterised by a high rate of TP53 mutations and often have deficient homologous recombination and repair of double-strand DNA breaks. This deficiency has led to promising new treatment approaches with PARP inhibitors, both as a single agent and in combination with cytotoxic drugs. So far, analogue-targeted approaches for type I ovarian carcinomas have not been established, although this subgroup is also characterised by distinct molecular alterations. In many of them, there is a constitutive activation of the MAP-kinase signalling pathway because of mutations in ERBB2, KRAS, or BRAF.