“This study suggests that high-throughput genomics could improve outcomes in a subset of patients with hard-to-treat cancers. Although these results are encouraging, only 7% of the successfully screened patients benefited from this approach.”
In the WINTHER trial, 107 patients with heavily pre-treated, solid tumor, advanced cancer usedFoundationOne®’s assay to identify targeted therapies based on tumor DNA sequencing. If FoundationOne® did not enable a treatment decision, RNA sequencing was used to find treatments targeting dysregulated gene expression. The following six case studies from the trial illustrate that Omicure’s unique RNA based approach to matching the right treatment to the right patient at the right time shows great promise.
Patient 2263, is a 29-year old woman whose head and neck adenocarcinoma had metastasized to her lung and lymph nodes. Her two prior lines of treatment were Carboplatin-Paclitaxel, and then, Tamoxifen. Because the DNA assay did not uncover any actionable genomic alterations, no therapies or clinical trials were recommended to her.
Then, RNA based analysis found several dysregulated genes, in particular, an over expression ofFGFR1, and suggested four VEGFR/FGFR Inhibitors (BGJ398, Orantinib, PD 173074, and Ponatinib), and the ODM203 — also a VEGFR/FGFR Inhibitor — clinical trial. The patient's medical team recommended ODM203, she began therapy, and within a matter of a few months her disease had stabilized.
On the base line scan of her lung, the target lesion, a lymph node, measured 22 millimeters onSeptember 15th, 2015. By January 8th, 2016, the node had shrunk to 8millimeters, an 18% reduction, and her disease was labeled stable with a progression-free survival (PFS) ratio of 4,01 compared to her previous treatment protocols
A 46-year-old woman with rhabdomyosarcoma and subcutaneous metastases, Patient 2091, had cycled through four lines of treatment: first Cisplatin, Dactinomycin, Doxorubicin, Ifosfamide, Vincristine; next, Carboplatin, Cisplatin, Dactinomycin, Ifosfamide, Erbitux, 5-FU, and Vincristine; then, Vinorelbine; and finally,Vincristine, Irinotecan, Temozolomide.
FoundationOne® revealed a CDK4 genomic mutation, and two clinical trials targeting that mutation were surfaced. However, the information was not actionable, as, either the patient was not eligible, or the trials were not recruiting.
Then, RNA based analysis identified, among other dysregulated genes, an over-expression of FGFR family members, suggesting five different FGFR Inhibitors (BGJ398, Lucitanib, Orantinib, PD 173074, and Ponatinib). After treatment with Pazopanib the patient’s disease had stabilized and the result was a PFS ratio of 1,4.
Patient 3132, also a 59-year-old man, had renal cell carcinoma with metastases to the liver and abdominal cavity, and had completed two lines of treatment: first Sunitinib Malate, followed by Axitinib. As was the case for the above-mentioned patients, the DNA analysis did not reveal any actionable mutations.
For this patient, RNA analysis surfaced several dysregulated genes, including an over-expression of SERPINC1. The selective estrogen receptor modulator (SERM) Toremifene was recommended and the medical team decided to prescribe the SERM Tamoxifen, which is almost chemically identical. This resulted in a PFS ratio of 1,3 compared to his previous lines of treatment.
Patient 5211, a 74-year old man with colon cancer that had metastasized to his lung and liver had received five previous lines of treatment. First, Bevacizumab, plus Leucovorin Calcium (Folinic Acid), Fluorouracil, Oxaliplatin (FOLFOX); thenFOLFOX alone; then Leucovorin Calcium (Folinic Acid), Fluorouracil andIrinotecan Hydrochloride (FOLFIRI); then Cetuximab; and finally, Regorafenib.
DNA analysis identified six genomic alterations but no corresponding or actionable therapies.
RNA analysis revealed several dysregulated genes, including an over-expression ofTOP2A and VEGFA, and suggested the combination of Bevacizumab and Etoposide. This successfully resulted in a PFS ratio of 14.7 compared to Patient 5211’s previous regimens.
An 82-year old man with neuroendocrine cancer and liver metastases, patient 2148 had been on two previous lines of therapies: Interferon Alfa 2B; and the AXI-IIG-02 clinical trial. The DNA analysis did not surface any actionable mutations, however RNA analysis showed an over-expression of ATK2and ATK3, potential targets for six different PI3K/AKT/mTOR Pathway inhibitors.Patient 2148’s medical team opted for Everolimus (PI3K/AKT/mTOR Pathway inhibitor), which after treatment, resulted in a PFS ratio of 2,2.
Patient 2203, a 67-year old woman with neuroendocrine cancer in the gastrointestinal tract, and metastases to the liver and peritoneum, had been on one previous therapy: Axitinib accessed through the AXI-IIG-02 clinical trial.
As for Patient 2148, DNA analysis did not surface any actionable mutations for her, however RNA analysis showed an over-expression of ATK2 and ATK3, potential targets for six differentPI3K/AKT/mTOR Pathway inhibitors. Here too, the medical team selected thePI3K/AKT/mTOR Pathway inhibitor Everolimus, and treatment was successful, yielding a PFS ratio of 2,9 compared to Patient 2203’s previous therapy.
Metastatic cancer continues to be lethal with small 5 years survival rates. This is despite hundreds of existing and new therapies, an exponential increase in available scientific and clinical data, and the advent of precision oncology. By harnessing the power of RNA sequencing, AI, and life science databases, OmiCure™ has now the ability to dive deeper, identify complementary or novel actionable insights, and provide patients and their medical team with a wider range of treatment options.
These cases studies show that RNA based analysis report is rapidly becoming an invaluable decision aid for targeted cancer treatment. OmiCure’s RNA based analysis provides oncologists with specific, actionable information about their patients’ biomarkers, along with a list of suggested agents that target them either alone or in combination. When taken into consideration with existing knowledge — including patient history and condition, relative availability and cost of treatment, known side effects, etc. — OmiCure™ also empowers oncologists to integrate the results of the report into their practice and, going beyond the list of identified drugs, select therapies that best fit the molecular profile of their patient.
