The first ‘tumour agnostic’ immunotherapy drug approval by the TGA will allow the pembrolizumab (Keytruda) to be used for a range of less common cancers characterised by biomarker signatures for microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR).
Pembrolizumab is already indicated for treatment of cancers including melanoma, non-small cell lung cancer and lymphoma. The new pan-tumour indications include colorectal and a range of non-colorectal cancers
The regulator has given provisional approval for pembrolizumab to be used in adult and paediatric patients for the treatment of unresectable or metastatic MSI-H/dMMR tumours that have progressed following prior treatment and when there are no satisfactory alternative treatment options.
According to the TGA, the tumour-agnostic indication has been approved based on the pooling of data on objective response rate and response duration across multiple different tissue types in a single-arm trial.
It states that sample sizes were too small to provide data on clinical utility of the MSI-H/dMMR tests for each of the tissue types, individually.
“The assumption that MSI-H/dMMR status is predictive of the treatment effect of [pembrolizumab] for every tissue type has not been verified. Continued approval for this indication depends on verification and description of clinical benefit in the confirmatory trials,” the approval notification states.
The indication for MSI-H/dMMR colorectal cancers is for those that have progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.
According to a statement released by MSD Australia more than 20 different tumours types may display MSI-H and/or dMMR,including endometrial, gastric, small intestinal, pancreatic, cholangiocarcinoma, adrenocortical, mesothelioma, small-cell lung, cervical, neuroendocrine, thyroid, urothelial, brain, ovarian, prostate, retroperitoneal, salivary, sarcoma, testicular and tonsillar cancers.
Patients can be identified by path labs using dMMR and MSI testing.
Dr Stephen Kao, medical oncologist at the Chris O’Brien Lifehouse in Sydney said he welcomed the the listing, which meant it would be worthwhile for clinicians to consider looking for dMMR and MSI biomarkers in patients who had failed all other treatments .
However he told the limbic that although TGA approved, pembrolizumab was not reimbursed for the pan tumour indications, and this would mean difficult discussions with patients about equity of access, financial toxicity if compassionate access programs were not available.
He also noted that the biomarkers were only present in a small subset of people, such as about 10% of patients with colorectal cancer and 2-3% of patients with mesothelioma.
“But in patients who do have the biomarker, if you find it then, treatment with pembrolizumab can make a significant difference,” he said.