Immunotherapy comes to the fore in treatment of mRCC

Tuesday, 27 Jul 2021

Treatment of people with metastatic renal clear cell carcinoma (mRCC) has evolved rapidly over the last decade, according to a snapshot of Australian prescribing that highlights the increasing uptake of immune checkpoint inhibitors and newer tyrosine kinase inhibitors (TKIs).

A review of PBS data from March 2010 to March 2020 showed that sunitinib had remained the most common treatment prescribed across Australia for mRCC, but its popularity has waned since in 2012 following the availability of new TKIs and potential ICI options.

The review, conducted by clinicians at the Olivia Newton-John Cancer Wellness and Research Centre, Austin Health, and Department of Medical Oncology, Monash Health, Melbourne, showed that the TKI axitinib was prescribed for mRCC following its introduction on the PBS in 2015.

However in recent times there had been a downturn in axitinib prescriptions, coinciding with the increasing utilisation of cabozantinib since its PBS approval in May 2018.

In contrast, the utilisation of pazopanib was stable since until July 2018 – after which rates of prescribing increased.

The study authors said that upfront combined ICI therapy with induction ipilimumab and nivolumab had become the standard of care for patients with intermediate or high-risk mRCC, based on the results of the CheckMate-214 study released in 2018.

This had shown response rates of 42%, and with 10% of all patients achieving a radiological complete response (CR), maintained in most after four years follow up.

“What was previously considered an incurable disease may now yield durable remissions using immunotherapeutics – either alone or in combination with other agents,” they said.

Their review noted that ipilimumab had recently been added to the PBS schedule and its use as induction therapy with nivolumab was steadily increasing.

“The surge in ipilimumab and nivolumab prescribing after PBS approval for the combination in February 2019 indicates the immunotherapeutic era for mRCC management in Australia,” they wrote.

There was also a strong rationale for combining ICI with TKI, the authors argued, based on synergistic effects to attenuate the host immune response.

However, while there was emerging data for survival benefits with combination axitinib and either avelumab or pembrolizumab, compared to sunitinib monotherapy, neither combination was PBS approved.

The decision to use either combination ICI or ICI/TKI as first-line therapy would also requires the consideration of various factors, they suggested, such as balancing the  greater chance of a rapid response against the potential cost of reduced quality of life and pathologic complete response rates.

They cautioned that the increasing use of ICI for mRCC would present cost challenges, especially as clinicians may be reluctant to stop therapy that maintains quality of life for patients compared to traditional  cytotoxic agents or TKI – particularly regarding symptoms of fatigue, mucositis and hand-foot syndrome.

“Long-term treatment with these agents represents a substantial financial burden for the healthcare system. They also require ongoing support in chemotherapy day units with finite resources of chairs and supervising clinical staff,” they wrote.

They warned that financial and other access barriers may create treatment disparities between different jurisdictions and regions for people with mRCC, as already suggested for people living in areas such as the NT.

The findings are published in the Internal Medicine Journal

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