Use of sunitinib was explored again in the S-TRAC trial (ClinicalTrials.gov Identifier: NCT00375674).5 Here 615 patients were randomly assigned to 1 year of sunitinib or placebo after surgery. A significant improvement in disease-free survival was found for patients assigned to sunitinib compared with placebo. But similarly to the ASSURE trial, sunitinib carried higher rates of grade 3 to 4 toxicities.
“I think that sunitinib could be a good agent in the adjuvant setting but only in high-risk patients,” Dr Massari said. “But we will not know until we have overall survival data.”
Earlier this year, the phase 3 PROTECT trial (ClinicalTrials.gov Identifier: NCT01235962) did not show improvements in disease-free survival among patients assigned to 1 year of pazopanib compared with placebo.6 The starting dose was reduced from 800 to 600 mg to improve tolerability and the primary endpoint was adjusted to reflect this change.
The study did not meet its primary endpoint of disease-free survival. There was, however, a decrease in recurrence risk among patients who received the 800-mg dose.
Dr Massari said there are no data proving or disproving the usefulness of immunotherapy in locally advanced RCC. The EORTC 18071 trial (ClinicalTrials.gov Identifier: NCT00636168) of ipilimumab, a CTLA-4 inhibitor, in patients with resected stage III cutaneous melanoma showed significantly improved recurrence-free survival in favor of ipilimumab compared with placebo.
According to Dr Massari and colleagues, this study showed, generally speaking, the “possible clinical benefit of an immune-checkpoint inhibitor as an adjuvant treatment.”
Current clinical trials are exploring the use of immune checkpoint inhibitors in both the pre- and postoperative setting of RCC. Researchers eagerly await data from these trials.
- Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7-30. doi: 10.3322/caac.21332
- Massari F, Di Nunno V, Ciccarese C, et al. Adjuvant therapy in renal cell carcinoma. Cancer Treat Rev. 2017;60:152-7. doi: 10.1016/j.ctrv.2017.09.004 [Epub ahead of print]
- Belldegrun AS, Chamie K, Kloepfer P, et al. ARISER: a randomized double blind phase III study to evaluate adjuvant cG250 treatment versus placebo in patients with high-risk ccRCC—Results and implications for adjuvant clinical trials. J Clin Oncol. 2017;31(suppl).
- Haas NB, Manola J, Uzzo RG, et al. Adjuvant sunitinib or sorafenib for high-risk, non-metastatic renal-cell carcinoma (ECOG-ACRIN E2805): a doubleblind, placebo-controlled, randomised, phase 3 trial. Lancet. 2016;14;387(10032):2008-16. doi: 10.1016/S0140-6736(16)00559-6
- Ravaud A, Motzer RJ, Pandha HS, et al. Adjuvant sunitinib in high-risk renal-cell carcinoma after nephrectomy. N Engl J Med. 2016;8;375(23):2246-54. doi: 10.1056/NEJMoa1611406
- Motzer RJ, Haas NB, Donskov F, et al. Randomized phase III trial of adjuvant pazopanib versus placebo after nephrectomy in patients with locally advanced renal cell carcinoma (RCC) (PROTECT). J Clin Oncol. 2017;35(suppl).