A phase I trial of the new PI3K inhibitor SAR245409

This study examined whether SAR245409 is safe and effective when used in combination with erlotinib (Tarceva).

SAR245409 is a newly developed drug, belonging to a class of agents called PI3K inhibitors. PI3K is a specific molecular pathway which propagates cancer cell growth and spread. Inhibiting the PI3K pathway is thought to delay disease progression. In addition, since the PI3K pathway is closely related to the actions of EGFR (epidermal growth factor receptor), a protein responsible for cancer formation and growth, PI3K inhibitors are thought to increase the effectivity of EGFR blockers such as erlotinib.

This study included a total of 46 patients with various types of cancer expressing the EGFR protein, 37 of which had advanced inoperable lung cancer. All patients were previously treated with EGFR targeted therapies, such as erlotinib, but experienced cancer progression despite therapy. Patients received SAR245409 along with erlotinib in gradually increasing doses to determine the safety and effect of this drug combination.

Overall, 12 patients (37.5%) achieved stable disease state with combination treatment. However, most patients were unable to tolerate the planned dose of SAR245409 due to adverse effects. The most common adverse effects were diarrhea, skin rash, vomiting and fatigue. Only a single life-threatening adverse event (a stroke) was noted. The maximal tolerated dose of SAR245409 was 70 mg when received once daily, or 20 mg if received twice daily.

This study reported SAR245409 as potentially beneficial in delaying lung cancer progression when combined with erlotinib. However, the use of SAR245409 is significantly limited due to adverse effects.

PI3K inhibitors like SAR245409 show great promise in the treatment of advanced lung cancer, but toxicities must be overcome before larger trials can take place.