Ravaud A, et al. - In view of a potential favourable safety profile of axitinib (AX), researchers explored a phase I study combining everolimus (EV) and AX for solid tumours. Here safety and pharmacokinetics (PK) analysis studies supported the combination of AX and EV at a recommended dose for each drug at its standard level: AX 5 mg BID (twice daily) and EV 10 mg OD (once daily). Side-effects reported were in the range expected both in effect and severity.

Methods

• In an escalation phase I study, researchers enrolled patients (pts) with advanced cancers and investigated the safety of the combination.
• They performed pharmacokinetic profile and functional vascular imaging.
• They explored an extension to pts with naive metastatic renal cell carcinoma (MRCC).

Results

• This study included 15 pts over three different dose levels (DLs); DL 0: AX 3 mg BID (twice daily)/EV 5 mg OD (once daily); DL 1: AX 5 mg BID/EV 5 mg OD and DL 2: AX 5 mg BID/EV 10 mg OD for 28 d.
• In this study, one dose-limiting toxicity (DLT) was reported at DL 0: grade (Gr) III diarrhoea and one DLT at DL 2: Gr III asthenia.
• In two pts, three severe adverse events (AEs) were encountered: jaw osteonecrosis, recurrent renal failure and cardiomyopathy.
• Level 2 was identified as the maximum tolerated dose (MTD).
• Gr III or Gr II AEs of interest after 1st cycle were mainly asthenia, diarrhoea and anorexia.
• Tumour shrinkage was observed in all pts except one.
• Researchers observed partial responses (PRs) in one pt with bladder carcinoma and in one pt in 1st line MRCC in the escalating phase.
• In the extension phase in naive MRCC treated at MTD, five pts indicated a PR and one pt indicated a prolonged stable disease.