Low-Dose Nivolumab in Renal Cell Carcinoma: A Real-World Experience

Breakthroughs in cancer research continue to improve the treatment outlook for patients across the various tumor types. In recent years, the approval of immune checkpoint inhibitors (ICIs) has positively improved patient outcomes while balancing a reasonable toxicity profile. However, access to these ICIs has been limited due to their high cost especially in healthcare settings where patients either co-pay or shoulder the entire healthcare cost. Outside the setting of clinical trials, these ICIs such as nivolumab are beyond the financial reach of the majority of patients, especially at the approved drug doses. Drug dosing in oncology is a complex subject matter with multiple considerations such as patient safety, drug efficacy, and business-economic considerations which differ in priority to the various stakeholders namely the patients, the healthcare providers, and the pharmaceutical companies. For example, from the patient’s perspective, the ideal drug dose has the lowest cost, with the best efficacy and the best safety profile. However, while patient safety and efficacy are of equal priority to pharmaceutical companies, achieving both at the lowest possible cost to the patient may not be the immediate focus.

While a lower drug dose may have a better drug and financial toxicity profile, it may however result in lower drug efficacy. But in healthcare settings where financial barriers preclude access to these high-cost medications, a lower drug efficacy may even be accepted in exchange for access to these medications with proven survival benefits. In reality, oncologists have been giving lower doses of ICIs according to what the patient can afford. This was done with the knowledge of the efficacy of lower doses that have been published in earlier CheckMate trials. However real-world evidence about this common practice has been lacking and hence we aimed to bridge this knowledge gap.

In this paper, we present our data on lower dosing of the single-agent nivolumab in advanced renal cell carcinoma (RCC). Our results suggest that there was no apparent reduction in efficacy. Although heterogeneity and inadequacy of data forestalled a definitive conclusion, our results seem comparable to those in published clinical trials and are also consistent with the pharmacologic data in dosing studies.

A parallel can be drawn between the use of lower dose ICIs presented in this study and the use of lower dose abiraterone in combination with food in patients with metastatic prostate cancer. Similar patient outcomes are achieved with 250mg of abiraterone taken with a meal as compared to the approved 1000mg dose on an empty stomach thereby reducing the cost to the patient to a quarter of the original cost. This has led to the recent inclusion of low dose abiraterone with food as a valid option in the National Comprehensive Cancer Network (NCCN) guidelines for metastatic prostate cancer.¹ Furthermore, a recent study surveying oncologists in India has shown that this has positively impacted patient access to abiraterone among patients with prostate cancer.²

In that same vein, formal randomized, placebo-controlled studies should be undertaken to assess this signal of equivalent efficacy with low dose nivolumab in metastatic RCC. While tedious, costly, and likely to be investigator-initiated, such a study will be immensely beneficial as it will improve patient access to ICIs as well as reduce healthcare costs. This will benefit both patients who co-pay/self-pay and healthcare systems that provide universal care.

The prospect of maintaining efficacy with lower and more affordable nivolumab dosages, with consequent improvements in accessibility to ICIs, leads us to look forward to further rigorous investigation in this field.

Written by: Joseph J Zhao, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

Nesaretnam Barr Kumarakulasinghe, MBBS, MRCP (UK), Associate Consultant, Department of Haematology-Oncology, National University Cancer Institute, Singapore

Natalie Ngoi, MBBS (Hons), MRCP (UK), M.Med (Int Med), Associate Consultant, Department of Haematology-Oncology, National University Cancer Institute, Singapore

Alvin SC Wong, MBBS, MRCP (UK), Senior Consultant, Department of Haematology-Oncology, National University Cancer Institute, Singapore

References:

National Comprehensive Cancer Network: Prostate Cancer, 2019. http://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf
Patel, Amol, Ian F. Tannock, Priyanka Srivastava, Bivas Biswas, Vineet Govinda Gupta, Atul Batra, Sainath Bhethanabhotla et al. "Low-dose abiraterone in metastatic prostate cancer: Is it practice changing? Facts and facets." JCO global oncology 6 (2020): 382-386.

Read the Abstract

Login