Ruxolitinib for Cancer Cachexia

Lung cancer patients on a whole, and a significant percentage of NSCLC patients in particular, develop cancer cachexia. In fact, approximately 30-40% of all NSCLC patients will develop cachexia in their disease course, with the highest percentages in stage IV patients. One-third of these patients will die of cachexia-related morbidity. In these groups, stage-matched NSCLC patients with cachexia will have poorer survival than those without cachexia. The JAK 1/2 inhibitor ruxolitinib has been used in many types of non-oncologic and oncologic patients with a well-established toxicity profile. Ruxolitinib was created as an oral agent with the capacity to antagonize JAK/STAT signaling across cell types. Based on the findings of the REACH2 and REACH3 trials, a starting dose of 10 mg twice daily oral administration of ruxolitinib was established for the latter patient population and is also a starting dose for the polycythemia patients. Known but manageable side effects of ruxolitinib use include thrombocytopenia, anemia, neutropenia, risk of infection, among other conditions. Ruxolitinib has not specifically been used in 1) cancer cachexia patient populations in an evaluable trial or 2) in the setting of first line cancer therapies for solid tumors who are receiving new standards of care including immunotherapy (IO). Therefore, in this trial, investigators propose using ruxolitinib in an open-label approach to antagonize systemic and tissue-specific, tumor-directed JAK/STAT signaling as a means curtailing cachexia progression in stage IV NSCLC patients. This study will ensure an acceptable toxicity profile when ruxolitinib is used in cancer cachexia patients.The use of ruxolitinib dose escalation in the same patients with frequent tissue and serum collections will permit us to better understand how important JAK/STAT signaling is to clinical cancer cachexia development.