Promising new advanced TNBC drug accessible for NZ women – at a cost

Results of a small but interesting trial of pembrolizumab (Keytruda) for advanced triple negative breast cancer (TNBC) were released in the USA recently.

Of the 27 TNBC patients in the KEYNOTE-012 study, many of whom had received multiple prior chemotherapies for their advanced cancers, 5 women (18.5%) responded to the drug. One patient had a complete response, and four had a partial response. Seven patients (26%) remained stable.

The median time to response was 18 weeks (range: 7-32 weeks). At the time of analysis, the median duration of response had not been reached with three of five responders on therapy for 11 months or more (range: 15-40+ weeks). At six months, the progression-free survival rate with KEYTRUDA was 23.3%.

Women in the study were patients with advanced TNBC whose tumours tested positive for PD-L1 expression (pembrolizumab is an anti-PD-1 therapy). 58% of patients screened for the study had PD-L1-positive tumours.

The most common treatment-related adverse events (side-effects), occurring in ≥5% of patients, included arthralgia, fatigue, myalgia, nausea, ALT increased, AST increased, diarrhoea, erythema and headache. Grade 3-5 treatment-related adverse events occurred in a total of five patients and included anaemia, disseminated intravascular coagulation (DIC), headache, meningitis aseptic, decreased blood fibrinogen, and pyrexia. Two patients discontinued treatment due to adverse events. One treatment-related death was reported in a patient with rapidly progressive disease and was due to DIC with thrombocytopenia and decreased blood fibrinogen.

What does this mean for NZ women?

Pembrolizumab is available to any patient/practitioner under Section 29 of the Medicines Act, which permits the sale or supply of unapproved medicines. So, if your oncologist thinks you might be a fit for pembrolizumab, he or she can prescribe it. The first step is likely to be PD-L1 testing, since the study was conducted on patients whose tumours tested positive for the PD-L1 protein. That testing is not to our knowledge available in NZ, though that is likely to change. At the moment, samples would need to be sent to Australia. Either way, the patient would need to pay for it.

The bad news: Pembrolizumab isn’t publicly funded in NZ. Its maker MSD expects to seek regulatory approval this from Medsafe this year – that approval is required before MSD can apply for Pharmac funding. But even if Pharmac decides to fund it – and pembrolizumb isn’t cheap, so it may not – that approval would most likely be just for melanoma, until more robust research data is available for other tumour types.

So, if pembrolizumab stacks up as a potential therapy for you, you’ll need to pay for it yourself. The current price per 3-weekly infusion is upwards of $10,000, though that’s likely to drop once supply can be sourced from Australia (hopefully by mid-2015). And with pembrolizumab designated as a “breakthrough” drug by the FDA, there’s likely to be more research released, which might help secure public funding at some stage. Note that while time-to-response in the KEYNOTE-012 trial averaged 18 weeks, the range was 7-32 weeks. That variation will likely present a dilemma for patients considering whether to commit to paying large sums every three weeks when it might take some time to know if it’s working.

Read more about anti-PD-1 therapies

Read the press release about the pembrolizumab / TNBC study from drug company MSD