SWOG 1500: Cabozantinib ‘new standard’ for metastatic papillary RCC
medwireNews: Cabozantinib offers significantly longer progression-free survival (PFS) than sunitinib for patients with metastatic papillary renal cell carcinoma (pRCC), the SWOG 1500 investigators say.
The phase 2 study findings were presented at the 2021 Genitourinary Cancers Symposium by Sumanta Pal (City of Hope Comprehensive Cancer Center, Duarte, California, USA) and simultaneously published in The Lancet.
“SWOG 1500 is the first randomized trial exclusively in patients with metastatic pRCC to complete accrual,” he said, explaining that the study explored the efficacy of MET inhibition in patients with type I and type II disease that is often associated with MET mutations versus VEGFR inhibition with the current standard of care sunitinib.
Overall, 152 patients with histologically confirmed pRCC and up to one prior line of therapy, excluding sunitinib, were randomly assigned to receive one of four regimens:
- cabozantinib 60 mg/day;
- sunitinib 50 mg/day on a 4-week on, 2-week off schedule;
- crizotinib 250 mg twice daily;
- orsavolitinib 600 mg/day.
However, the prespecified futility analysis after 15 PFS events in each experimental arm and 20 events in the sunitinib arm led to closure of the crizotinib and savolitinib arms, Pal said.
By contrast, PFS was significantly longer with cabozantinib than sunitinib, at a median of 9.0 versus 5.6 months and a hazard ratio of 0.60 in the one-sided analysis. Pal remarked that the 95% confidence interval of 0.37–0.97 suggests “that our findings would remain significant if we had proposed a two-sided test.”
The study design included local and central assessment of pRCC histology and showed some discordance, with 13 type II locally assessed patients classified as type I centrally and three type I patients classified as type II.
But Pal emphasized that “irrespective of central or local assessment, patients with type I and type II disease appeared to have benefit with cabozantinib.”
Cabozantinib also achieved a significantly higher confirmed objective response rate (ORR) than sunitinib (23 vs 4%). Two patients experienced a complete response, both of whom were treated with cabozantinib.
Preliminary overall survival (OS) analysis did not detect a significant difference between the cabozantinib and sunitinib arms, at a median 20.0 and 16.4 months, respectively, and follow-up is continuing, Pal said.
The presenter reported that toxicity in the SWOG 1500 trial was similar to that observed in large studies of the agents, with grade 3–4 adverse events occurring in 74% of cabozantinib-treated patients and 68% of those given sunitinib. Treatment was discontinued because of treatment-related adverse events in 24% and 23% of the groups, respectively.
Pal concluded that “cabozantinib had a homogeneous treatment effect across” pRCC subtypes and therefore “should be considered the new reference standard for systemic therapy in patients with metastatic pRCC.”
Session discussant Stephanie Berg (Loyola University Chicago, Illinois, USA) reviewed the SWOG 1500 findings and said that “we should consider cabozantinib as another first-line option for papillary kidney cancer.”
She compared the results with those from the phase 3 SAVOIR trial of patients with MET-driven pRCC, which failed to show a significant improvement in PFS with savolitinib versus sunitinib, despite achieving numerically better OS and ORRs.
Questioning whether the savolitinib arm in SWOG 1500 might have performed better had the patients been selected for MET mutations, Berg concluded that “we’ll have to wait for further exploratory analysis regarding MET mutation status to tease out these differences.”
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