Evaluation of chromosome 17 (Chr-17) polysomy in Her2 FISH-negative metastatic breast cancer (MBC) patients enrolled in a randomized phase III study of paclitaxel and lapatinib
Researchers believe that having multiple copies of a cromosome (i.e. 3 or more, a condition known as polysomy), specifically of chromosome 17, may result in higher expression of Her-2, thus leading to a greater response when treated with Her-2 inhibitors, such as lapatinib. This study evaluated whether women with Her-2 negative tumors who had chromosome 17 polysomy would derive a benefit from lapatinib.
Unfortunately, no statistically significant difference in progression-free survival was seen between the various groups. The authors conclude that women with Her-2 negative tumors will not derive any benefit from Her-2 inhibitors, regardless of the status of chromosome 17.
The CONCEPT trial (Combined Oxaliplatin Neuropathy Prevention Trial) was designed to study patients with mCRC receiving Oxaliplatin/ Bevacizumab as 1 st line treatment, and to evaluate whether giving oxaliplatin intermittently (IO) in a regimen of FOLFOX/Bevicizumab would reduce cumulative neurotoxicity, and therefore allow patients to stay on treatment longer than those receiving a conventional Oxali schedule (CO). The authors also explored the impact of calcium and magnesium (CaMg) administration on neurotoxicity.
Patients were randomly assigned to receive either standard FOLFOX given every 2 weeks (CO) or FOLFOX alternating with 5-FU/Leucovorin and bevacizumab (IO group). Each group was further divided so that half received calcium (Ca) and magnesium (Mg) infusions and half received a placebo in an attempt to decrease neurotoxicity.
Many studies do a review of the results partway through, so that the study can be stopped if one group is doing much better. This study was stopped early because the investigators felt that the groups receiving Ca/Mg were having poorer responses to therapy. Critics have pointed out that the evaluation of response was not confirmed and was done by the investigator, who may have been biased. While the study has been stopped, further analysis continues into the responses.
Despite stopping early and having a smaller-than-planned sample size; the group receiving intermittent (IO) oxaliplatin did have better responses to therapy. Progression-free survival (that is, survival with no recurrence) was 12 months in the IO group versus 7.3 months in the CO group. In addition, the incidence of severe neurotoxicity was improved, 24% (CO) versus 10% (IO). And this toxicity also corresponded with a need for dose reductions, leading to more dose reductions in the CO group.
Despite the early termination of the study, the IO regimen appears to achieve the goal of keeping patients on therapy longer, and the Ca/Mg infusions appear to reduce neurotoxicity, also leading to better treatment adherence. Further study is needed to determine if the study was stopped prematurely, so stay tuned.