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9071 Background: BRG is a kinase inhibitor approved for the treatment of patients (pts) with ALK+ metastatic NSCLC; specific details for BRG use vary by indication and country. We report long-term efficacy and safety results of the Phase 1/2 and Phase 2 (ALTA) trials of BRG. Methods: The Phase 1/2 study was a single-arm, open-label trial (NCT01449461) of BRG 30–300 mg/d in pts with advanced malignancies. ALTA (NCT02094573) randomized pts with CRZ-refractory ALK+ NSCLC to receive BRG at 90 mg qd (arm A) or 180 mg qd with 7-d lead-in at 90 mg (arm B). For the Phase 1/2 study, investigator assessments of confirmed objective response rate (cORR; RECIST v1.1), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety in pts with ALK+ NSCLC are reported. The primary endpoint of ALTA was cORR per investigator; secondary endpoints included cORR per independent review committee (IRC), DoR, PFS, and OS. Results: In the Phase 1/2 study, 137 pts received BRG; of these, 79 pts had ALK+ NSCLC (71/79 had prior CRZ; 28/79 received 180 mg qd [7-d lead-in at 90 mg]; 14/79 received 90 mg qd). In ALTA, 222 pts with CRZ-refractory ALK+ NSCLC were randomized (n = 112/110, arm A/B). At the end of the Phase 1/2 study (Feb 18, 2020), with median 27.7 mo follow-up (̃67 mo after last pt enrolled), 4 pts remained on BRG. At the end of ALTA (Feb 27, 2020), with median 19.6/28.3 mo follow-up in arm A/B (̃53 mo after last pt enrolled), 10/17 pts in arm A/B were still on treatment. Table shows efficacy results from final analyses with long-term follow-up. In ALTA, the IRC-assessed intracranial cORR in pts with measurable baseline brain metastases was 50% (13/26) in arm A and 67% (12/18) in arm B; Kaplan-Meier (KM) estimated median intracranial DoR was 9.4 mo (95% CI, 3.7, not reached [NR]) in arm A and 16.6 mo (3.7, NR) in arm B. With long-term follow-up, no new safety signals were identified. Treatment-emergent adverse events led to dose interruption (Phase 1/2: 59%; ALTA arm A/B: 49%/61%), dose reduction (13%; 8%/33%), or discontinuation (10%; 4%/13%). Conclusions: BRG showed sustained long-term activity, PFS, and manageable safety in pts with CRZ-refractory ALK+ NSCLC. The 180 mg/d dose after 7-d lead-in at 90 mg/d led to numerically higher median PFS and OS. Final results are similar to those reported for other approved ALK tyrosine kinase inhibitors in this setting. Clinical trial information: NCT01449461, NCT02094573. [Table: see text] more...

e20014 Background: Correct staging of small cell lung cancer (SCLC) in limited disease (LD) or extensive disease (ED) is crucial as it has an impact on the therapeutic decision-making. The staging procedures in SCLC in the late 1990s included chest X-ray, blood samples, abdominal ultrasonography (UL), and iliac crest BMex. The aim of this study was to evaluate the continued eligibility of performing BMex in patients (ptt) with SCLC as a routine staging procedure, and to see how often therapeutic decisions were influenced by a positive BM before and after the PET/CT scan era. Methods: All diagnostic and staging procedures were registered in ptt with SCLC referred to our department from 1995 to 1999 in cohort 1 (C1). Cohort 2 (C2) included SCLC patients referred from 2009 to 2013. In C2 results of PET/CT in terms of bone metastases were related to results of BMex. Results: In C1 194 ptt was referred with 136 (70%) having ED. BMex was omitted in 32 (17%) fragile ptt having known ED while all LD ptt underwent BMex. BM involvement was seen in 37 (23%) of all 162 BMex and 36% of the 104 ED ptt examined. When BM was negative the staging of ED was due to other imaging. The BM had an impact on therapeutic decision-making in 5 (4%) of 136 having ED and 5 (3%) of 162 BMex. In C2 211 ptt of 292 (72%) had ED and 203 (70%) of all ptt underwent BMex. BM biopsy was done in 137 (65 %) ED and in 66 (69 %) LD. Of 137 ED ptt BM involvement was found in 31 (23 %) cases. A PET/CT scan was performed in 13 (42 %) of these ptt of which bone metastases was found in 12 (92 %). One patient (8%) had a PET/CT without bone lesions. Bone metastases were seen at PET/CT scan in 61 ptt in C2, of these 22 (36%) had negative BM, whereas 12 (20%) had BM involvement and in 3 ptt (5%) BMex were inconclusive. No BMex was performed in 24 ptt (39%). BMex had an impact on therapeutic decision-making in 3 (1.4%) of 211 having ED and 5 (2.5%) of 203 BMex. Conclusions: Due to staging by PET/CT and CT scan in SCLC ptt the impact of BMex in the therapeutic decision-making has decreased and fewer ptt are undergoing BMex. Though a negative PET/CT cannot exclude BM involvement BMex may be considered omitted. more...

e20503 Background: Most ALK+ NSCLC patients (pts) receiving CRZ eventually experience disease progression. Based on promising activity in a phase 1/2 trial, a randomized phase 2 trial of the ALK inhibitor BRG in pts with CRZ-refractory, advanced ALK+ NSCLC (ALTA; NCT02094573) was initiated. Responses and adverse events (AEs) varied with starting dose; therefore, ALTA was designed to evaluate 2 distinct BRG regimens. Methods: Pts were stratified by presence of baseline (BL) brain metastases and best response to prior CRZ and randomized 1:1 to receive BRG at 90 mg qd (arm A) or 180 mg qd with a 7-d lead-in at 90 mg (arm B). Primary endpoint was investigator-assessed confirmed objective response rate (ORR) per RECIST v1.1. Results: In 222 pts (arm A/B, n=112/n=110), median age was 51/57 y; 71%/67% had brain metastases. As of May 31, 2016, 51%/56% (A/B) continued to receive BRG; median follow-up was 10.2/11.0 mo. Table shows efficacy. In pts with measurable BL brain metastases (A/B, n=26/n=18), confirmed intracranial ORR was 46%/67%. Most common treatment-emergent AEs (A/B) were: nausea 36%/43%, diarrhea 21%/39%, cough 23%/36%, headache 28%/30%, vomiting 28%/26%; grade ≥3 AEs included increased CPK 3%/10%, hypertension 6%/6%, pneumonia 3%/5%, increased lipase 5%/3%. A subset of pulmonary AEs with early onset (median: Day 2) occurred in 14/219 (6%) treated pts (3%, grade ≥3); 7/14 pts were successfully retreated. Dose reductions (8%/23%, A/B) and discontinuations (3%/10%) due to AEs were reported. Conclusions: BRG showed substantial activity, robust PFS, and acceptable safety at both dose levels, with numerically improved efficacy (particularly PFS and intracranial ORR) at 180 mg (with lead-in). Clinical trial information: NCT02094573. [Table: see text] more...

9007Background: We report the first results of a pivotal ph 2 trial of BRG in pts with ALK+ NSCLC. BRG, an investigational oral tyrosine kinase inhibitor (TKI) with preclinical activity against rea... more...

7091 Background: Hyponatriemia is very often seen in SCLC due to the paraneoplastic syndrome SIADH. Hyponatriemia has been found to be associated with poorer outcome in some but not in the majority of published studies. This study was performed to investigate the prognostic value of hyponatriemia in SCLC. Methods: Data from the patient files from 468 patients diagnosed with SCLC and treated at Odense University Hospital 1995 to 2005. In the 444 cases data on the initial S-Na was available. A Cox multivariate analysis was performed including possible prognostic factors. Results: Stage: Extensive disease (ED) 283 (64%), limited disease (LD) 161 (36%). The standard chemotherapy was 6 cycles of carboplatin-etoposide. 70% of the patients with LD received thoracic radiotherapy, usually in a dose of 45 Gy/22–30 F and 49% received PCI usually as 25 Gy/11F. Median survival in ED 7.2 months with a 1 and 2-year survival rate of 21% and 6%. In LD the figures was 15.2 months, 65%, 31% and a 5-year survival rate of 16%. S-Na was [Table: see text] No significant financial relationships to disclose. more...