Introduction: Pembrolizumab has shown clinical benefit in patients with previously treated recurrent or metastatic SCLC in the phase 1b multicohort study KEYNOTE-028 (NCT02054806) and the phase 2 multicohort study KEYNOTE-158 (NCT02628067). We present a pooled analysis of patients from KEYNOTE-028 and KEYNOTE-158 who had received two or more lines of previous therapy for SCLC.Methods: Eligible patients were aged 18 years and above, had histologically or cytologically confirmed incurable recurrent or metastatic SCLC, had an Eastern Cooperative Oncology Group performance status of 1 and below, and had received two or more lines of previous therapy. Patients in KEYNOTE-028 were required to have a programmed death ligand 1 (PD-L1)-positive tumor. Patients received pembrolizumab (10 mg/kg every 2 weeks in KEYNOTE-028 or 200 mg every 3 weeks in KEYNOTE-158) for up to 2 years. The primary end point was objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1, which is presented here per independent review. Results: Eighty-three patients who had received two or more lines of previous therapy (KEYNOTE-028, n ¼ 19; KEYNOTE-158, n ¼ 64) were included. Median follow-up duration was 7.7 (range, 0.5-48.7) months. Objective response rate was 19.3% (95% confidence interval: 11.4-29.4); two patients had complete response (one with a PD-L1-positive tumor), and 14 patients had partial response (13 with PD-L1-positive tumors). The median duration of response was not reached (range, 4.1-35.8þ mo; plus sign indicates ongoing response); 61% of responders had responses lasting 18 months or longer. Fifty-one patients (61.4%) experienced any-grade treatment-related adverse events; eight patients (9.6%) had grade 3 or higher events.Conclusions: Pembrolizumab exhibited durable antitumor activity in a subset of patients with recurrent or metastatic SCLC who had undergone two or more previous lines of therapy, regardless of PD-L1 expression. Pembrolizumab was well tolerated.
2020 Background: LM due to NSCLC progression are associated with poor prognosis. Osimertinib is an oral, CNS-active, irreversible EGFR-TKI selective for sensitizing (EGFRm) and T790M resistance mutations. Methods: In the BLOOM study (NCT02228369), pts with EGFRm advanced NSCLC who had progressed on prior EGFR-TKI therapy and had LM confirmed by positive cerebrospinal fluid (CSF) cytology received osimertinib 160 mg once daily (qd). Response was assessed (by investigator) in 2 cohorts: T790M unselected and T790M positive (by central test); results are presented as a combined analysis set. Analyses were based on CSF cytology, brain MRI imaging, and neurological examination every 6 weeks (wk; relative to first dose) until progression. Adverse events (AEs) were graded according to CTCAE. EGFR-mutant DNA in CSF was determined by ddPCR. Plasma and CSF samples were collected for PK analyses. Results: As of 24 Sep 2016,32 pts had received treatment: 21 T790M unselected; 11 T790M positive. Max treatment duration was 17.5 months (m; median 6.0 m); 21 pts ongoing. 23/32 pts had a 12-wk brain image assessment: 10 had radiological improvement, 13 had stable disease (SD). The same 23 pts had a 12-wk neurological assessment: of 8 symptomatic pts, 7 improved, 1 had SD; of 15 asymptomatic pts, 2 worsened, 13 remained asymptomatic. The geometric mean decrease in EGFR-mutant DNA copy was 57% (95% CI 30, 74) in 22 pts with pre-dose and Cycle 2 Day 1 CSF samples. Most common AEs were skin effects (n = 20), diarrhea (n = 13), nausea (n = 11) and paronychia (n = 9). All were grade (G) 1/2 except 1 case each of diarrhea and nausea (both G3). 9 pts had dose interruptions and 4 had dose reductions to 80 mg qd. Osimertinib mean concentration in CSF was 7.51 nM (range 2.19–21.1 nM) at steady state (N = 16); CSF:free plasma ratio: 16%. Accrual is now complete (n = 41; 21 T790M unselected, 20 T790M positive) and updated data (including overall survival) will be presented. Conclusions: Osimertinib penetrates the blood-brain barrier. Encouraging activity and manageable tolerability in pts with LM from EGFRm NSCLC was observed at 160 mg qd, with a median treatment duration of 6.0 m; continued evaluation is ongoing. Clinical trial information: NCT02228369.
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