Erlotinib Is Not Effective In Patients (Pts) With JAK-2 V617F Positive Polycythemia Vera

Erlotinib is an epidermal growth factor receptor small-molecule inhibitor and is FDA approved for the treatment of lung and pancreatic cancers. In preclinical study, in vitro colony culture assays revealed that erlotinib at micro-molar concentrations effectively suppressed the growth and expansion of Polycythemia Vera (PV) hematopoietic progenitor cells while having little effect on normal cells. Several JAK inhibitors are being studied for the management of PV, one of which has been approved for the treatment of myelofibrosis (ruxolitinib).

To study the clinical effect of erlotinib in pts diagnosed with JAK2V617F + PV.

We conducted a single arm, prospective phase II study at the University of Oklahoma and the Oklahoma City VA hospitals in pts with WHO defined JAK-2 V617F positive PV from June 2010 to August 2012. Appropriate IRB approval was obtained in accordance with Hilsinki declaration. Pts had to be requiring phlebotomy. Toxicity was assessed by treating physicians using NCI version 4. Dose modification for erlotinib was done using label recommendations.

Five Caucasian pts were enrolled (3 (60%) males, with median age at enrollment of 63 years, range 26-79). Pts had pretreatment median hemoglobin14.4 g/dL (10.4 -19.2 g/dL), median platelet count 511 x10⁹ (424-681 x10⁹), median white blood cell (WBC) 14.4 x10⁹(7.8- 18.3 x10⁹). Three pts had splenomegaly prior to treatment. Median number of prior pharmacologic treatments (hydroxyurea, anagralide or interferon) was 1, range 0-2. Pts were given erlotinib 150 mg orally daily for 16 weeks: responders (phlebotomy free or decrease in spleen size) were allowed to continue a total of 1 year of treatment, while non-responders were taken off the study. Three (60%) patients received therapy for 16 weeks and did not achieve hematological response or improvement in spleen size. Two (40%) pts were taken off the study after 2 doses secondary to severe toxicities (grade 3 colitis in 1 case, and grade 3 facial rash in 1case). No therapy continued beyond 16 weeks (due to toxicity or lack of response). All pts in the study developed rash (grade 1 – 3) and diarrhea (grade 1 – 2). Three pts developed mucositis (see Table 1). No death was observed during the study and follow up period (median follow up was 23 months, range 12-37 months). Study was closed due to lack of efficacy.

Despite in vitro efficacy of erlotinib as potent inhibitor of JAK-2 activity, erlotinib is not effective in pts with JAK-2 V617F positive PV with poor toxicity profile. Poor accrual was related to potential toxicity of erlotinib compared to alternative treatments in view of lack of clinical efficacy.

No relevant conflicts of interest to declare.