Nintedanib associated with comparable effectiveness, fewer adverse events than sunitinib in RCC

CHICAGO — Nintedanib exhibited similar effectiveness as sunitinib in previously untreated patients with advanced renal cell carcinoma but was associated with lower frequency of stomatitis and dermatologic adverse events, according to results of a phase 2 study presented at the ASCO Annual Meeting.

Additionally, nintedanib (BIBF 1120, Boehringer Ingelheim) was not associated with QT prolongation.

Previous trials have established sunitinib (Sutent, Pfizer) as a standard first-line therapy for patients with advanced RCC. However, treatment can be restricted by the incidence of drug-related adverse events.

“Antiangiogenic agents are effective in renal cell cancer, but we also know that current agents are associated with significant toxicities. For example, roughly 20% of patients starting on sunitinib will discontinue it as a result of adverse effects,” Tim Eisen, PhD, FRCP, of the department of oncology at Addenbrooke Hospital in Cambridge, United Kingdom, said during a press conference.

Eisen and colleagues conducted the current study to evaluate the efficacy and safety of nintedanib in 96 patients with previously untreated, advanced, unresectable/recurrent clear cell RCC.

Researchers randomly assigned 64 patients to nintedanib 200 mg twice daily, given in 4-week cycles. The other 32 patients received sunitinib 50 mg once daily (4 weeks on, 2 weeks off).

The study design provided a control for the variability of response and efficacy but was not powered for a full comparison between nintedanib and sunitinib, according to researchers. 

Patients continued treatment until disease progression or unacceptable drug-related adverse events. PFS at 9 months served as a primary endpoint, as did corrected QT interval change from baseline to day 15 in patients treated with nintedanib.

Secondary endpoints included PFS, objective response rate, OS, time to progression, time to treatment failure and adverse events.

According to study results, PFS at 9 months was not statistically significantly different between patients treated with nintedanib (43%) and those treated with sunitinib (45%; P=.85). The researchers also found no statistically significant disparities between nintedanib and sunitinib with regard to:

• PFS (median 8.44 months vs. 8.38 months; HR=1.16; 95% CI; 0.71–1.89);
• Confirmed ORR (18.8% vs. 31.3%; P=0.19);
• OS (median 20.37 months vs. 21.22 months; P=0.63);
• Time  to progression (median 8.48 months vs. 8.54 months; P=0.52); or
• Time to treatment failure (median 8.41 months vs. 8.36 months; P=0.46).

“Nintedanib does display evidence of effectiveness in a 200 mg twice daily dose and exhibits a manageable safety profile that is similar to sunitinib in this exploratory study,” Eisen said. “However, I would emphasize that this is based on exploratory data and is not powered to make direct comparisons.”

Grade 3 adverse events occurred in 47% of patients assigned to nintedanib compared with 56% assigned to sunitinib. Common adverse events included diarrhea (61% vs. 50%), nausea (38% vs. 34%), fatigue (25% in both arms) and vomiting (16% vs. 22%). Additionally, dermatologic adverse events were less frequent with nintedanib than sunitinib (8% vs. 47%).

“Given these results, the question is whether it is worth developing these agents further in clinical studies. In my opinion, there is no unselected first-line signal from nintedanib but we can’t exclude a signal in a selected group,” Eisen said. “Where you have a patient with a tumor in which FGF signaling is essential, then it would be possible that agents such as this could have an important role to play.”

For more information:

Eisen TMS. Oral Abstract Session #4502. Presented at: ASCO Annual Meeting; May 31-June 4, 2013; Chicago.

Disclosure: The researchers report consulting or advisory positions with, as well as research funding and honoraria from, Astellas Pharma, AstraZeneca, AVEO, Bayer, Boehringer Ingelheim, GlaxoSmithKline and Pfizer.