Could terminal patient’s recovery after organoid assay mean better ovarian cancer treatments?

More ovarian cancer patients could be treated successfully after organoid testing enabled one woman’s remarkable recovery from terminal cancer.

The “dramatic clinical response” came after the precision medicine company SEngine tested the organoids grown from the patient’s low grade serious ovarian cancer (LGSOC) tumour against a panel of 42 small molecule drugs. The study coordinators selected the 42 from their wider library of more than 240 therapeutics, “based on standard-of-care chemotherapies, drugs targeting common cancer genes and pathways for LGSOC, and the genomic profile of the patient’s tumor, which included a CHEK2 mutation”.

The process led to ibrutinib – a Bruton’s tyrosine kinase (BTK) inhibitor with no history of efficacy against ovarian cancer – being identified as the most potent potential therapy. Although ibrutinib is not an FDA-approved treatment for this cancer type, the 52-year-old Gulf War veteran’s oncologist requested its off-label use after receiving the assay results. “To our knowledge,” said the authors of the woman’s case report, “this is the first report indicating the use of ibrutinib… to treat chemotherapy-resistant ovarian cancer (and) resulting in clinical benefit.”

The patient was reported to be in rapid decline and unable to eat at the time the assay was carried out, and had already undergone paclitaxel and carboplatin chemotherapy, as well as two operations. But the ibrutinib monotherapy led to her leaving hospice care and achieving 15 months of stable disease, in addition to no longer requiring opioid-based pain management. After 65 weeks on ibrutinib, she started to progress and was given afatinib – another drug that had scored highly during the organoid-drug matching process, and which prevented tumour progression for another 44 weeks when used as a second monotherapy. Overall, this meant that the woman achieved more than two years of stable disease because of ibrutinib and afatinib treatment combined, compared to the median progression-free survival period of 7.2 months. According to the case report, the patient subsequently experienced anaemia and rising levels of the tumour marker CA-125 and was switched to erlotinib, another Epidermal Growth Factor Receptor inhibitor identified by the assay. Her response to erlotinib was being assessed at the time of case report’s publication.

The case report is heartening not only as a story of individual recovery, but also because organoid drug screening platforms like the SEngine PARIS test used here could lead to better future treatments for LGSOC patients. LGSOC is the rarer form of Epithelial ovarian cancer (EOC), the most lethal cancer of its type, and typically responds poorly to chemotherapy. This explains LGSOC patients’  generally poor prognosis, and means that the development of new approaches is a matter of urgency.

As well as noting the links between high BTK expression and reduced overall survival rates in ovarian cancer patients, the case study authors claimed that they had demonstrated: “the clinical utility of organoid-based drug sensitivity testing to identify personalized and actionable treatments.”

“Patient-derived tumor organoids… retain histological and biological features and somatic genomic alterations from the originating tumor,” they added.

“But (they) also share the entire germline genomic profile, as well as any exposure or treatment history, all of which can affect drug sensitivity and response to therapy.

“Controlling for these variables could, in theory, enhance the predictive accuracy of patient-derived organoid models relative to other cancer models that are genetically unrelated to any given patient.”

Dr Carla Grandori, one of the authors of the case study, said the research team was “overjoyed by the progress this patient has made over more than two years.

“Her remarkable turnaround reaffirms the power of our approach, and further, helped us identify a cohort of ovarian cancer patients likely to respond to similar precision treatments.”