Many people with CML start treatment with a second-generation medication, such as Sprycel or Tasigna, because they more potently suppress the proliferation of leukemia cells. But how do these two medications compare?
A group of researchers looked at this issue twice. They analysed clinical trial data for Sprycel (the DASISION study) and Tasigna (the ENESTnd study) as a way of indirectly comparing the two drugs (a direct comparison hasn’t been made) (Signorovitch and colleagues. Curr Med Res Opin 2011;27:1263-1271). All participants in the studies were newly-diagnosed and had not yet received any treatment. After matching similar individuals before the start of treatment, they found that more people taking Tasigna achieved a major molecular response (MMR; or a 3-log reduction in BCR-ABL transcripts) after one year of treatment compared to those taking Sprycel (56.8% vs. 45.9). Overall survival rates at one year were also slightly higher with Tasigna (98.8% vs. 97.3%).
The same group has now looked at how well people did on the two therapies over the first four years of treatment (Signorovitch and colleagues. Curr Med Res Opin 2015;31:315-322). About 8% more people taking Tasigna achieved a deep molecular response (a 4-log or 4.5-log reduction) compared to those on Sprycel after one year of treatment. This better response was maintained for four years. However, it’s important to note that people did very well with both medications, and a similarly low proportion of people progressed to accelerated-phase or blast-crisis CML with the second-generation medications over the course of four years.
Two other studies have also examined this question. A review of eight studies involving over three thousand people found that people taking Tasigna and Sprycel were about three-fold more likely to have a complete cytogenetic response (CCyR) in the first six months of treatment, and about twice as likely to achieve MMR after one year compared to those taking Gleevec (Mealing and colleagues. Exp Hematol Oncol 2013;2:5). doi: 10.1186/2162-3619-2-5). Tasigna and Sprycel appeared to be comparably effective in this analysis.
A CML clinic in China reviewed patient records to see how well people had done with Tasigna, Sprycel and Gleevec (Wang and colleagues. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2015;23:356-363). A difference in treatment response were seen within the first three months, with a higher proportion of people achieving CCyR with Tasigna and Sprycel (53%, 55%) compared to those taking Gleevec (33%). The difference was especially noticeable for MMR rates: 9-11% at three months with the second-generation drugs compared to only 1% with Gleevec. This “response gap” never closed. At 12 months, the CCyR rate was 88% with Tasigna, 86% with Sprycel and 69% with Gleevec. The 12-month MMR rate was 49-50% with the second-generation drugs compared to 28% with Gleevec. The risk of progressive disease was also twice as high with Gleevec (8%) compared to the other two medications (4-5%).