CHICAGO — Sunitinib improved radiographic PFS compared with everolimus among certain subgroups of patients with metastatic non–clear cell renal cell carcinoma, according to findings from a phase 2 trial presented at the ASCO Annual Meeting.

However, patients assigned sunitinib (Sutent, Pfizer) also demonstrated greater rates of grade 3 or worse toxicities, results showed.

This study marks the first time researchers identified an mTOR-sensitive subgroup of patients with non–clear cell renal cell carcinoma compared with VEGF inhibition in the front-line setting.

Andrew J. Armstrong, MD, ScM,an associate professor of medicine and surgery in the division of medicine-oncology at the Duke University School of Medicine, and colleagues conducted the ASPEN trial — an international, randomized trial — to compare sunitinib with everolimus (Afinitor, Novartis) in 108 patients (median age 63 years; 75% men) with metastatic non–clear cell renal cell carcinoma who had papillary (66%), chromophobe (15%) or unclassified (19%) histology and no prior systemic therapy. Most patients and intermediate-risk disease (59%), 27% had good-risk disease and 15% had poor-risk disease.

Radiographic PFS — measured using RECIST 1.1 criteria — served as the primary endpoint.

Researchers expected 90 PFS events to occur, resulting in an 83% power to detect a 38% decrease in the HR for progression or death.

Researchers stratified patients by their histology and risk group and randomly assigned them to the everolimus arm (n = 57) or sunitinib arm (n = 51).  The treatment arms were balanced at baseline.

After 87 PFS events, 53 deaths and two patients still on treatment, sunitinib met the primary endpoint by improving PFS.

Patients in the sunitinib arm achieved a median PFS of 8.3 months (80% CI, 5.8-11.1), whereas the median PFS in the everolimus arm was 5.6 months (80% CI, 5.5-6; HR = 1.41; 80% CI, 1.03-1.92).

Sunitinib specifically improved PFS compared with everolimus in patients considered good risk (14 months vs. 5.7 months; HR = 3.07; 80% CI, 1.51-6.28) or intermediate risk (6.5 months vs. 4.9 months; HR = 1.38; 80% CI, 0.96-2). Researchers also observed improved PFS with sunitinib vs. everolimus in patients with papillary (8.1 months vs. 5.5 months; HR = 1.52; 80% CI, 1.05-2.2) or unclassified histology (11.5 months vs. 5.6 months; HR = 2.55; 80% CI, 1.01-6.45).

However, everolimus improved PFS compared with sunitinib in poor-risk patients (6.1 months vs. 4 months; HR = 0.21; 80% CI, 0.06-0.69) and patients with chromophobe histology (11.4 months vs. 5.5 months; HR = 0.71; 80% CI, 0.31-1.65).

Sunitinib improved median OS compared with everolimus (31.5 months vs. 13.2 months); however, the improvement did not reach statistical significance (HR = 1.17; 95% CI, 0.65-2.14).

Although no unexpected safety signals emerged from the treatment, sunitinib did result in more grade 3 or worse treatment-related adverse events than everolimus (65% vs. 47%).

“Patients with metastatic non–clear cell renal cell carcinoma treated with sunitinib had a statistically significantly prolonged PFS duration compared with patients treated with everolimus,” Armstrong said during his presentation. “Sunitinib resulted in improved PFS both in good- and intermediate-risk patients and papillary and unclassified histologies, whereas everolimus resulted in improved PFS in both poor-risk and chromophobe subtypes.

“Future trials in this heterogeneous collection of diseases should consider these factors when designing prospective studies. Both agents resulted in short PFS times and low response rates illustrating the unmet need still in this population for better drugs to improve PFS and OS.” – by Anthony SanFilippo

Reference:Armstrong AJ, et al. Abstract 4507. Presented at: ASCO Annual Meeting; May 29-June 2, 2015; Chicago.

Disclosure: Armstrong reports honoraria, research funding and travel expenses from; consultant/advisory and speakers bureau roles with Astellas, Bayer, Bristol-Myers Squibb, Dendreon, ImClone Systems, Janssen Biotech, Janssen Oncology, KangLaiTe, Medivation, Novartis, Pfizer and Sanofi. See the abstract for a list of all other researchers’ relevant financial disclosures.

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