210MO - Low dose nivolumab with TKI in mRCC: Dosing strategies, de-escalation and survival among self-paying patients in India

Background

Nivolumab with TKI is an accepted treatment option for metastatic RCC (mRCC).However, nivolumab at currently licensed doses remains unaffordable in India where most patients pay out-of-pocket. We evaluated the practice patterns and clinical outcomes with low dose nivolumab combined with TKI in a tertiary academic hospital in India.

Methods

Consecutive mRCC patients treated with nivolumab and TKIs between December 2019 and December 2022 were included. Due to variations in nivolumab dosing frequencies, we used dose/Kg/14 days for comparative analysis. The survival impact of treatment de-escalation due to financial or drug toxicity was evaluated. PFS, OS were calculated as per standard definitions and adverse events graded as per CTCAE4.1.

Results

We identified 57 patients who received nivolumab and TKI with 38(63.2%) IMDC intermediate and 15(26.4%) poor prognoses. The mean age was 53.1±8 years, male (82%), non-clear cell histology in 16(28%). Common metastatic sites were osseous (43.9%), pulmonary (73.7%), CNS 8(10.2%) and Liver15(26.3%). Forty-six (80.7%) received no prior systemic therapy. The median Nivolumab dose was 0.88 mg/kg/14days (IQR0.4-1.4), commonly dosed as 40mg every 21-28 days. The TKIs used were Lenvatinib (47.4%), cabozantinib (49.1%). At 12 months median follow-up, the PFS of 31 patients who received <1mg/kg/14days (ULD) of Nivolumab was 11 months versus 23 months among the 25 patients receiving >1mg/kg/14days (LD) (p=0.39). The median OS was NR vs 25 months (P= 0.51). The one-year PFS and OS was 35.5% vs 42.3% and 45.2% vs 53.8% for ULD vs LD respectively. Most (68.4%) underwent treatment de-escalation due to financial toxicity 28(43.9%) or drug toxicity 11(19.3%) without any detriment to PFS or OS (1year PFS and OS with and without de-escalation was 46% vs 22.2% and 56.4% vs 33.3% respectively). Grade 3&4 adverse events were palmoplantar dysesthesia 10(17.5%), hypertension 8(14%). Primary hypothyroidism 28(52.8%) was the commonest grade 2 AE.

Conclusions

LD nivolumab with TKI did not result in inferior survival although the efficacy of ULD could not be confirmed. Treatment de-escalation due to financial toxicity was common. LD strategies in mRCC warrant prospective trial evaluation.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.