Nivolumab+cabozantinib demonstrates durable efficacy for renal cancer

 

“Long-term updates [are warranted to] establish durability of clinical benefits with immunotherapy-based regimens,” noted Dr Robert Motzer from the Memorial Sloan Kettering Cancer Center, New York, New York, US, in his poster presented at ASCO GU 2021. “[Moreover,] there is a historical unmet need for improved treatment options for [sRCC,] … an aggressive histologic [aRCC] subtype associated with poor prognosis.”

 

In the primary analysis, first-line NIVO+CABO demonstrated superiority over sunitinib in terms of progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) after a minimum follow-up of 10.6 months. [ESMO 2020, abstract 6960]

 

Participants were 651 adults (median age 62 years, 74 percent male) with previously untreated aRCC, who were randomized 1:1 to receive NIVO 240 mg IV Q2W + CABO 40 mg QD, or sunitinib 50 mg QD (4 weeks of 6-week cycles). [ASCO GU 2021, abstract 308]

 

In the intention-to-treat (ITT) analysis, at a median follow-up of 23.5 months, survival benefit was still significantly greater with NIVO+CABO vs sunitinib (median, 17.0 vs 8.3 months; hazard ratio [HR], 0.52; p<0.0001 [PFS] and median, not reached [NR] vs 29.5 months; HR, 0.66; p=0.0034 [OS]), as was the ORR (54.8 percent vs 28.4 percent).

 

NIVO+CABO also led to a higher complete response (CR) rate (9.3 percent vs 4.3 percent), shorter time to response (TTR; 2.8 vs 4.2 months), and longer duration of response (DOR; 21.7 vs 12.7 months) than sunitinib.

 

About three-quarters of participants reported grade ≥3 all-cause adverse events (AEs) with both NIVO+CABO and sunitinib (78.4 percent vs 73.1 percent). Grade ≥3 treatment-related AE rates were 62.2 percent vs 52.5 percent, respectively, the most common being hypertension.

 

Discontinuation rates owing to TRAEs were 9.7, 7.2, 6.6, and 9.1 percent for NIVO, CABO, NIVO+CABO, and sunitinib, respectively. There were reports of death deemed treatment-related in both the NIVO+CABO and the sunitinib arms (n=1 and 2, respectively).

 

Thirty-four NIVO+CABO recipients were sRCC-positive (sRCC+), while the rest were classified as sRCC-negative (sRCC–). In the sunitinib arm, 41 were sRCC+; the remaining 287 comprised the sRCC– cohort.

 

As in the ITT analysis, survival benefit and ORR among sRCC+ individuals were better with NIVO+CABO vs sunitinib (median, 10.3 vs 4.2 months; HR, 0.42 [PFS], median, NR vs 19.7 months; HR, 0.36 [OS], and 55.9 percent vs 22.0 percent [ORR]).

 

The sRCC– arm also had remarkable PFS (median, 17.5 vs 9.2 months; HR, 0.56), OS (median, NR for both; HR, 0.73), and ORR benefits (54.7 percent vs 29.3 percent) with NIVO+CABO vs sunitinib.

 

More NIVO+CABO recipients had CRs regardless of sRCC status (8.8 percent vs 2.4 percent [sRCC+] and 9.3 percent vs 4.5 percent [sRCC–]). As in the ITT population, the NIVO+CABO arm also had shorter TTR (median, 2.8 vs 3.9 months and 2.8 vs 4.4 months, respectively) and longer DOR (median, 18 vs 8.3 months and 21.7 vs 13.3 months, respectively) vs the sunitinib arm.

 

The fraction of sRCC+ participants achieving a ≥30-percent reduction from baseline tumour burden was also greater in the NIVO+CABO vs the sunitinib arm (73 percent vs 41 percent), which mirrors the rates observed in the ITT analysis (71 percent vs 43 percent).

 

No new safety signals were observed in this patient subgroup.

 

The sustained survival benefit with NIVO+CABO reflects its durable efficacy, which remained even in the presence of sarcomatoid features, noted Motzer and colleagues. The AE profile of NIVO+CABO also correlated with those reported for each drug, with no new safety signals reported. “These results continue to support NIVO+CABO as a potential new first-line treatment option for patients with aRCC.”