More than half of
patients with non–small cell lung cancer and KRAS mutation assigned
to sorafenib had no progression at 6 weeks, but that did not translate into
improved survival, according to recently released results from a single-arm
phase 2 study.
The reported rate of non-progression at 6 weeks was
52.6% for patients assigned to daily sorafenib (Nexavar, Bayer). Median PFS was
2.3 months, and median OS was 4.9 months.
“There is a great need for targeted treatment
options for patients with non–small cell lung cancer with a KRAS
mutation,” Wouter W. Mellema, MD, said in a press release. “Sorafenib
could be a useful drug in this patient population by inhibiting the
growth-stimulating signal of the RAS protein. However, although sorafenib
showed relevant activity, the outcome was unsatisfactory.”
Mellema, a doctoral candidate at VU University Medical
Center in Amsterdam, presented the results at the AACR-IASLC Joint Conference
on Molecular Origins of Lung Cancer: Biology, Therapy and Personalized Medicine
in San Diego.
In the study, 57 patients were assigned to 400 mg daily
sorafenib. The median duration of treatment was 9 weeks, and the median
duration of response was 32 weeks.
Twenty-one patients required dose modifications, four of
whom discontinued treatment. Fifteen patients discontinued treatment before 6
weeks, 10 of those for clinical progression.
Mellema said two patients were still on treatment and 14
were still alive.
Five patients reported grade-3 skin toxicity, four had
grade-3 gastrointestinal toxicity and one patient had both grade-3 metabolic
abnormalities and a grade-3 pneumonitis. The most common adverse events
included fatigue (6.4%), hand-foot reaction (5.7%) and dyspnea (5.6%).
For more information:
- Mellema WW. #PR5. Presented at: the 2011
AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer: Biology,
Therapy and Personalized Medicine; Jan. 8-11, 2012; San Diego.
In the absence of a placebo or
chemotherapy control group, we cannot say that progression was, in fact,
delayed. The data in PFS and OS, especially in the absence of RECIST criteria
responses, does not encourage further study of sorafenib as a single agent in
Miguel A. Villalona, MD
Director of Solid Tumor Experimental Therapeutics
Division Director of Medical Oncology
The Ohio State University
Comprehensive Cancer Center
Disclosure: Dr. Villalona reported receiving past
research funding from Onyx Pharmaceuticals.