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Background CDK4/6 inhibitors (CDK4/6i), in combination with aromatase inhibitors, are United States Food and Drug Administration-approved for the treatment of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (MBC). The effectiveness of continuing them beyond first disease progression (PD) is currently unknown. This retrospective study evaluated the impact of the continuation of CDK4/6i beyond first PD in HR+/HER2− MBC using real-world experience. Patients and Methods A single-institution retrospective review of patients with HR+ MBC who received CDK4/6is from 2015 to 2018 and where CDK4/6is were continued beyond first PD. The primary outcome was progression-free survival (PFS) after initial PD on CDK4/6i therapy. Results Thirty women with HR+/HER2− MBC met eligibility criteria. Patients were identified from a prospective database of patients at the Cleveland Clinic Foundation who were prescribed CDK4/6is. The median age and follow-up duration were 47.5 years and 27 months, respectively. Most patients received palbociclib (PA)/letrozole as initial therapy (67%), followed by PA/fulvestrant (23%), and PA/other aromatase inhibitor (20%), and abemaciclib with either fulvestrant or letrozole (6%). As of January 31, 2019, 25 (83.3%) patients were still alive, and 19 (63%) patients had progressed. The estimated median PFS for continued CDK4/6i use beyond the first PD was 11.8 months (95% confidence interval, 5.34-13.13 months). Conclusions Among a small cohort of patients with HR+ MBC in a non-clinical trial setting, continuation of CDK4/6i-endocrine treatment post initial PD was associated with a median PFS of about 12 months. Formal randomized clinical trials evaluating the continuation of CDK4/6is beyond the first PD are currently ongoing and will provide more answers to this important clinical question.

Real-world data are critical to demonstrate the reproducibility of evidence and external generalizability of randomized clinical trials. Palbociclib is an oral small-molecule inhibitor of cyclin-dependent kinases 4 and 6 that has been shown to improve progression-free survival (PFS) when combined with letrozole or fulvestrant in phase 3 clinical trials. We evaluated real-world outcomes in metastatic breast cancer patients who received palbociclib in combination with endocrine therapy in routine clinical practice. Records of patients with advanced hormone receptor (HR)-positive breast cancer treated with palbociclib at the Cleveland Clinic health system from February, 2015 to December, 2017 were retrospectively reviewed. The primary end point was PFS. In this cohort, 411 women were included. The median age and follow-up times were 53.5 years and 10.2 months, respectively. The median PFS for palbociclib plus letrozole was 15.1 months for patients treated in first line, 10.5 months in second line, and 4.2 months in third line and beyond. For patients who received fulvestrant plus palbociclib, the median PFS in first, second, and third line and beyond were 11.6, 12.3, and 6.4 months, respectively. The most common adverse events were hematologic, with grade 3–4 neutropenia occurring in 58% of patients. Thirty-one (8%) patients permanently discontinued palbociclib due to adverse events. Among patients with HR-positive advanced breast cancer, the estimated PFS in patients treated with fulvestrant and palbociclib was comparable to a previously reported phase 3 trial. However, the median PFS with letrozole and palbociclib was shorter than previously reported data from phase 2 and 3 trials. Palbociclib toxicity was very manageable, with a low drug discontinuation rate.

Pure red cell aplasia (PRCA) is characterized by normocytic normochromic anemia, severe reticulocytopenia, and a total absence or marked reduction of erythroid precursors in the bone marrow. It can...

A 24-year-old African-American man presented with malaise and low back pain and was found to have acute severe rhabdomyolysis followed by acute hemolysis. Glucose-6-phosphate dehydrogenase (G6PD) deficiency was suspected by the presence of blister cells on peripheral smear and was confirmed by a low enzyme activity assay. Our patient reported playing football, along with upper respiratory infection symptoms, prior to presentation. Extensive infectious and toxicology workup was negative; however, several inflammatory proteins were markedly elevated. We hypothesized the large inflammatory burden led to an increased reactive oxygen radical burden that overwhelmed muscle and erythrocyte reducing power. Severe rhabdomyolysis in G6PD deficiency is not a common presentation because skeletal muscles are more resistant to oxidative damage compared to red blood cells. Our case adds to the few existing reports of myolysis in the setting of G6PD deficiency.

e17570 Background: IMRT for HNSCC limits exposure to critical nearby structures thereby reducing toxicities. Real world data on toxicities after long term follow-up post IMRT for HNSCC are lacking. This study assessed the incidence of late toxicities in patients with HNSCC within 5 years post-treatment with definitive IMRT (d-IMRT). Methods: This is a retrospective, IRB approved, single-institution review of patients (pts) with stage I-IVB HNSCC treated with d-IMRT +/- chemotherapy between 2009 and 2013. The primary outcomes were incidence of severe late toxicities (dysphagia requiring esophageal stricture dilation, physician-reported grade 2 or worse neck fibrosis and xerostomia) occurring 3 months or more after completion of IMRT; feeding tube (FT) dependence within 1st year of IMRT completion, and FT dependence beyond 1st year post IMRT. Toxicities were deemed acute if they occurred during IMRT and up to 90 days post IMRT. Results: 274 pts, median age 59 years (38 – 82.9), were identified. 67.6% were HPV positive, 10.5% HPV negative and HPV status was unknown in 21.9%. Site of disease was oropharynx in 70%, larynx in 25% and hypopharynx in 4%. 206 pts (75.2%) received d-IMRT alone, 37 (13.5%) had definitive concurrent chemoradiation – mostly with cisplatin (58%), and 31 (11.3%) received adjuvant IMRT. Of the 243 pts treated with d-IMRT +/- chemotherapy, 80 (32.9%) required FT during RT due to grade 2 or worse acute dysphagia. Excluding 11 pts with disease recurrence or new HNSCC diagnosis, FT dependence at any time from 3 months to one year post IMRT occurred in 22 of 232 pts (9.48%), while FT dependence beyond 1st year post IMRT occurred in 8 pts (3.4%). 11 pts (4.7%) required stricture dilation for late dysphagia. Late grade 2 or worse fibrosis and xerostomia occurred in 7 (3.0%) and 89 (38.4%) pts, respectively. Conclusions: Our study suggests that except for xerostomia, severe late toxicities after definitive IMRT for HNSCC is likely uncommon. Prospective studies with late IMRT toxicities and their impact on quality of life (QoL) as endpoints are warranted.

e12538 Background: CDK inhibitors (CDKi), in combination with aromatase inhibitors (AI), are approved for the treatment of hormone receptor positive (HR+) Her2 negative metastatic breast cancer (MBC). The effectiveness of continuing CDKi beyond first disease progression is not known. This study evaluated real world evidence and assessed the impact of continuation of CDKi beyond first disease progression in combination with endocrine therapy. Methods: This is a retrospective, single institution review of HR+ MBC patients treated with CDKi from 2015-2018 who continued CDKi after initial progression. The primary outcome was progression-free survival (PFS) beyond first disease progression, as assessed by the clinician based on radiological and/or clinical criteria. Overall survival (OS) – defined as date of initial CDKi treatment to date of death or last follow up – was a secondary outcome. Results: 30 women with HR+/HER2- MBC, median age 47.5 years (range: 31 – 81), sequentially continued on CDKi beyond first progression were identified from a database of patients treated with Palbociclib. Median and average follow up times on CDKi were 27.18 and 24.53 months, respectively. Initial endocrine/CDKi regimen received included: palbociclib (PA)/letrozole (LTZ) [67%], PA/fulvestrant (FULV) [23%], and PA/other AI [10%]. Prescribed combinations beyond 1st progression were: PA/FULV [56.7%], PA/LTZ [16.7%], and PA/other AI [20%], abemaciclib plus LTZ or FULV [6%]. As of 1/31/2019, 25 patients (83.3%) were still alive, and 19 (63%) had undergone a second progression on CDKi. The estimated median PFS for the entire duration while on CDKi was 23.5 months (95% CI 12.8 – 27.8), of which 11.8 months (95% CI 5.34 – 13.13) was the median PFS beyond first progression. The estimated median OS was 45.4 months. Conclusions: Among a small cohort of HR+ MBC patients, in a non-clinical trial setting, continuation of palbociclib plus endocrine therapy beyond first progression was associated with a median PFS of approximately 11 months. Formal clinical evaluation of continuation of CDK inhibitor plus endocrine therapy beyond first progression is warranted.

e13034Background: Palbociclib (PA), a CDK4/CDK6 inhibitor, has been shown in clinical trials to prolong progression free survival (PFS) in HR+/Her-2 negative MBC when combined with an aromatase inh...