Rare cancer patients may benefit from immunotherapy, but access an issue


By Mardi Chapman

18 Nov 2021

Dr Oliver Klein

Immunotherapy has an emerging role in the management of patients with advanced rare cancers, but access is an ongoing challenge, oncologists have told the 2021 COSA ASM,

Dr Oliver Klein from the Olivia Newton John Cancer Research Institute and Austin Health, Victoria, said rare cancers combined make up about 20-25% of all cancer diagnoses.

There was clearly an unmet medical need given rare cancers typically had a poor prognosis and inferior survival compared to more common malignancies.

“Immunotherapy using checkpoint inhibition has clearly transformed the treatment algorithms in a range of different cancers and in particular the durability of response with these agents is impressive. We wanted to make these treatments available to patients with rare cancers,” Dr Klein said.

Dr Klein, , presented findings from the multicenter open-label phase II CA209-538 clinical trial of nivolumab plus ipilimumab in rare gynaecological cancers (n=43), upper GI cancers (n=41) and neuroendocrine tumours (n=36).

Induction treatment was four doses of ipilimumab and nivolumab every three weeks and two years of maintenance with nivolumab monotherapy.

He said the objective response rate was about 30% across all three groups of rare cancers.

“Another 30% of patients have achieved stable disease. As we would expect with immunotherapy…treatment response was durable in many patients.”

Dr Klein said some patients with partial remission on the week 12 scans evolved into complete remission beyond two years and after discontinuation of study treatment.

The study found no unusual immune toxicities and there was no evidence of any treatment- related deaths.

Grade 3/4 irAEs including hepatitis, enterocolitis and hypercortisolism were reported in 28% of patients.

The results from the subgroup of patients with rare gynecological cancer have been published in The BMJ.

Looking ahead

Dr Klein said the biomarker analysis component of the study was still underway but results on tumour mutational burden (TMB) were inconsistent with a meta-analysis which had previously found a correlation between TMB and response to checkpoint inhibition.

“In our patient cohort we could not see any difference between responders and patients with stable disease or progressive disease with the median TMB.”

He noted the vast majority of patients in the study had a fairly low mutational burden which is in keeping with what is described for these tumour histologies in the literature.

“TMB as a sole biomarker is certainly of no value in this patient population to predict response.”

He said the encouraging response rates from patients and high interest from clinicians to enrol patients in the trial warranted an Australia-wide study which is underway.

Informed by the initial study, the MoST-CIRCUIT study (CA209-6D6) will focus on patients with rare cancers most likely to respond including neuroendocrine tumours, biliary tract cancers, gynaecological malignancies and mismatch repair protein deficient cancers excluding colorectal cancer.

However, a later panel discussion at COSA 2021 in which Dr Klein participated heard that access to subsidised immunotherapy was a major challenge for patients with rare cancer. The small numbers of patients meant it was difficult for sponsors to gain evidence of cost effectiveness to satisfy PBS reimbursement criteria, the panel was told.

In many cases the only way patients could access new treatments was through clinical trials or compassionate access programs, the panel heard.

Dr Klein said a key problem was the lack of biomarkers that could predict which patients with rare cancers would respond to a particular immunotherapy.

“These medications are very expensive and they are not available at the moment outside of trials. So it’s obviously a very difficult decision when you have these discussions with patients [with rare cancers] knowing that there are potentially life saving treatments that are not accessible, and there’s a lack of interest from the commercial world to develop these medications in this patient population,” he said.

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