Results from the Phase III LUME-colon 1 trial (NCT02149108), presented last week at the ESMO 2016 Congress in Copenhagen (Denmark), have indicated that nintedanib improves progression-free survival (PFS), but not overall survival (OS), for metastatic colorectal cancer (mCRC) patients unresponsive to standard therapy.
Nintedanib is an anti-angiogenic multiple tyrosine kinase inhibitor. The LUME-colon 1 trial is the first Phase III trial to evaluate the drug in otherwise-refractory mCRC patients.
A total of 768 patients defined as having good organ function and performance status were randomized 1:1 to nintedanib or placebo. All received best supportive care, and the co-primary endpoints were PFS and OS.
Median PFS (1.5 vs 1.4 months) and disease control (26 vs 11%) were improved compared with placebo, yet there was no difference seen in OS. Serious adverse events occurred in 39% of patients taking the drug, with 14% discontinuing treatment. This compared with 35% of patients taking placebo exhibiting adverse effects and 11% discontinuing.
“Nintedanib was well tolerated and gave a significant increase in PFS which means that tumors stopped growing more frequently in patients taking the drug. But patients receiving nintedanib did not live longer, which was disappointing,” commented Eric Van Cutsem (lead author; University Hospitals Leuven, Belgium).
“The reason why patients on placebo survived longer than expected is not completely clear, but treatments taken after the trial that stopped their tumor from growing may have contributed to this finding,” he continued. “After the trial finished, patients were followed until death and these subsequent treatments may have diluted the effect of nintedanib, leading to a loss in potential survival benefit.”
Additional analyses are now being conducted on molecular markers and cancer subtypes in order to determine if there is a specific group of patients who could benefit from the drug.
With many mCRC patients becoming refractory to several different lines of treatment, there is a need to find new therapies. While nintedanib demonstrated good tolerability its effects could be considered disappointing.
“Nintedanib delays disease progression and increases the rate of stable disease but these gains are lost when it comes to OS,” noted Dick Arnold, Instituto CUF de Oncologia (Lisbon, Portugal). “This is in contrast to regorafenib and trifluridine/tipiracil which both showed increases in both PFS and OS in this line of treatment.” He believes the disparity may be due to more patients in this particular trial receiving salvage treatments than in earlier trials. Alternatively, he suggests nintedanib may simply not work well enough. “More data are needed to explain the findings and understand how strong the benefit of nintedanib really is.”