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Background The second-generation ALK tyrosine kinase inhibitor (TKI) ALC has demonstrated efficacy and acceptable safety in ALK+ NSCLC pts who have progressed on CRZ. However, resistance to ALC eventually develops, with secondary resistance mutations detected in approximately 50% of pts and a median progression-free survival (PFS) Trial design The second-generation ALK tyrosine kinase inhibitor (TKI) ALC has demonstrated efficacy and acceptable safety in ALK+ NSCLC pts who have progressed on CRZ. However, resistance to ALC eventually develops, with secondary resistance mutations detected in approximately 50% of pts and a median progression-free survival (PFS) Table . 1586TiP Primary Endpoint Blinded independent review committee (BIRC)−assessed PFS per RECIST v1.1 Secondary Endpoints BIRC-assessed intracranial PFS Overall survival Investigator- and BIRC-assessed ORR, time to response, and duration of response (DOR) BIRC-assessed intracranial ORR and DOR Safety/tolerability Health-related quality of life Selected Exploratory Endpoints BIRC-assessed CNS efficacy per Response Assessment in Neuro-Oncology Brain Metastases criteria (intracranial ORR, DOR, and PFS) Molecular determinants of efficacy and safety with BRG and ALC Clinical trial identification NCT03596866. Editorial acknowledgement Peloton Advantage, LLC, an OPEN Health Company; funded by Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. Legal entity responsible for the study ARIAD Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. Funding ARIAD Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. Disclosure S. Popat: Research grant / Funding (institution): Boehringer Ingelheim, Epizyme, BMS, Clovis Oncology, Roche, Lilly, Takeda; Honoraria (self): Boehringer Ingelheim, AstraZeneca, Roche, Takeda, Chugai Pharma; Advisory / Consultancy: Boehringer Ingelheim, Roche, Novartis, Pfizer, AstraZeneca, BMS, MSD, Guardant Health, AbbVie; Travel / Accommodation / Expenses: Boehringer Ingelheim, BMS, Merck Sharp & Dohme. G. Liu: Research grant / Funding (institution): Takeda, AstraZeneca, Roche, Bayer, Boehringer Ingerheim; Honoraria (self): Roche, Takeda, AstraZeneca, Bristol-Myers Squibb, AbbVie, Pfizer, Merck,Novartis, EMD Serano, Bayer; Advisory / Consultancy: Roche, Novartis, Pfizer. S. Lu: Advisory / Consultancy: AstraZeneca, Boehringer Ingelheim, Hutchison MediPharma, Simcere, Roche, JS InnoPharm; Speaker Bureau / Expert testimony: AstraZeneca, Roche; Research grant / Funding (self): AstraZeneca, Hutchison MediPharma. G. Song: Full / Part-time employment: Takeda. V. Samnotra: Full / Part-time employment: Takeda. J.C. Yang: Advisory / Consultancy: Boehringer Ingelheim, Eli Lilly, Bayer, Roche/Genentech/Chugai, Astellas, MSD, Merck Serono, Pfizer, Novartis, Celgene, Merrimack, Yuhan Pharmaceuticals, BMS, Ono Pharmaceutical, Daiichi Sankyo, Takeda, AstraZeneca, Hansoh Pharmaceuticals.

Summary. Two male first cousins with mild haemophilia A had baseline factor VIII levels of 12–15% and experienced bleeding requiring coagulation factor infusion therapy with trauma and surgical procedures. Both the patients with haemophilia A also had electrocardiographically documented symptomatic paroxysmal atrial fibrillation (PAF) for several years that had become resistant to pharmacological suppression. Radiofrequency ablation was considered in both the cases but deferred considering refusal of consent by the patients to undergo the procedure. Remission of arrhythmias has been reported in patients with iron-overload syndromes. Body iron stores assessed by serum ferritin levels were elevated in both men but neither had the C282Y or H63D genes for haemochromatosis. Calibrated reduction of iron stores by serial phlebotomy, avoiding iron deficiency, was followed by remission of symptomatic PAF in both cases. Iron reduction may be an effective treatment for arrhythmias apart from the classic iron-overload syndromes and deserves further study particularly in patients with bleeding disorders who might be at risk for arrhythmias and other diseases of ageing.

15527 Background: ACC is a rare malignancy with a very poor prognosis. Surgery is the only potential curative option. Gefitinib is an oral EGFR inhibitor that may have activity in solid tumors that express EGFR. ACC over expresses EGFR in a high proportion of cases. Methods: From April 2004 through December 2006, the ACC Working Group conducted a phase II trial of Gefitinib as second line, monotherapy in patients with pathologically confirmed unresectable ACC who had progressed on mitotane or chemotherapy. All prior systemic therapy was discontinued 28 days prior to starting gefitinib. Patients were ineligible if: had received prior therapy with any EGFR inhibitor, pregnant or breast feeding, had other co-existing malignancies (other than basal cell carcinoma or cervical cancer in situ), had an ECOG PS > 2, absolute neutrophil counts < 1,500, or platelets < 20,000. Patients were not allowed concomitant use of phenytoin, carbamazepine, rifampicin, barbiturates, or St John’s Wort. Patients took gefitinib 250 mg orally once a day. Each cycle was 21 days with radiological assessment every 6 weeks.Response rate as determined by RECIST criteria was the primary endpoint. Results: 19 patients accrued to the study (18 with measurable disease and 1 without). Pt Characteristics: Female 79% (15/19); Median age 48 (range 26–74); 84% (12 female and 4 male =15/19) of the patients had steroid secreting tumors. Grade 3 toxicity was noted in 2 patients and included, hypertension and lower extremity edema and elevated liver transaminases. No grade 4 toxicities occurred. Of 19 patients evaluable, there were no complete responders, partial responders or patients with stable disease (0% response rate; 95% CI: 0%-18%). Conclusions: Gefitinib demonstrated no activity in patients with unresectable ACC. This study is now closed. This study demonstrated the ability to successfully accrue to a trial of novel agents in rare tumors in a multicenter setting. [Table: see text]

4770 Background: Primary neoplasms of the adrenal cortex are extremely rare malignancies, estimated to represent 0.05–0.2% of all cancers diagnosed in the United States annually. These cancers carr...