exemestane in post-menopausal women with nsclc

Conditions: Non-Small Cell Lung Cancer

Summary: this is a phase ii therapeutic study of adding exemestane therapy in post-menopausal women with advanced non-small cell lung cancer (nsclc) who are progressing while on treatment with an immune checkpoint antibody (pembrolizumab, atezolizumab, or nivolumab).


Eligibility criteria:
inclusion criteria * recurrent or progressive advanced stage non-small cell lung cancer (no small cell component) with most recent treatment being an fda approved immune checkpoint inhibitor (pembrolizumab, atezolizumab, or nivolumab) note: pathology reports documenting the diagnosis of nsclc are required to be reviewed to confirm outside diagnosis * sufficient tumor tissue available from original diagnosis or subsequent biopsy for analysis of estrogen receptor and aromatase - tumor block or a minimum of 5 unstained slides * failed at least 1 prior fda approved treatment for advanced nsclc. patients with egfr/alk/ros1 rearrangements should have received an fda-approved tki prior to enrollment on this trial. * measureable disease by recist version 1.1 * post-menopausal defined as * age ≥ 55 years and 1 year or more of amenorrhea * age \< 55 years and 1 year or more of amenorrhea with an estradiol assay \< 20 pg/ml * surgical menopause with bilateral oophorectomy * ecog performance status 0, 1 or 2 \* life expectancy of 3 months or more in the opinion of the enrolling investigator and documented in the medical record * adequate organ function within 14 days of study enrollment defined as: * hematology: \*\* absolute neutrophil count (anc) ≥ 1500/mm³, platelets ≥ 100,000/mm³, hemoglobin ≥ 8 g/dl * biochemistry: * total bilirubin within normal institutional limits * ast/sgot and alt/sgpt ≤ 2.5 x upper limit of normal (uln), except if there is known hepatic metastasis, wherein transaminases may be ≤ 5 x institutional uln. * serum creatinine ≤ 1.5 mg/dl or glomerular filtration rate \> 50 ml/min * must have recovered to ctcae v 4 grade 1 or better from the acute effects of any prior surgery, chemotherapy or radiation therapy. chronic residual toxicity (i.e. peripheral neuropathy) is permitted. * a minimum time period must elapse between the end of a previous treatment and start of study therapy: * 1 week from the completion of radiation therapy for brain metastases * 4 weeks from the completion of chemotherapy or any experimental therapy * 4 weeks from prior major surgery (such as open biopsy or significant traumatic injury) * voluntary written consent before any research related procedures or therapy exclusion criteria * known active cns disease - if patient has history of brain metastases, the brain lesions must have been treated with radiation and/or surgery - patients should be neurologically stable and requiring ≤10mg oral prednisone equivalence of steroids per day * any toxicity from immune-related toxicity from prior immune therapy that would preclude further treatment with anti-pd-1/pdl-1 inhibitor or ongoing ir toxicity ≥ grade 2 * requiring \> 10 mg prednisone equivalence of steroids per day for immune-related toxicity * inability or unwilling to swallow study drug * any gastrointestinal condition causing malabsorption or obstruction (eg, celiac sprue, gastric bypass surgery, strictures, adhesions, history of small bowel resection, blind loop syndrome) * currently using hormone replacement therapy (oral or patch) or/and phytoestrogen supplements (i.e. black cohosh) * known hypersensitivity to exemestane or its excipients * any serious underlying medical condition that, in the opinion of the enrolling physician, would impair the ability of the patient to receive protocol treatment * prior malignancy, with the exception of curatively treated squamous cell or basal carcinoma of the skin or in situ cervical cancer, unless there is a 3-year disease-free interval * concomitant use of strong cyp3a4 inducers such as rifampicin, phenytoin, carbamazepine, phenobarbital, or st. john's wort as these may significantly reduce the availability of exemestane

Keywords: nsclc