Joseph L. Leach

3501 Background: Evidence supports use of nivolumab (N) in MSI-H mCRC. N, a fully human anti-PD-1 mAb and ipilimumab (I), a humanized anti-CTLA-4 mAb, have favorable safety & efficacy in other tumors. CheckMate-142, a phase 2 study, evaluates N ± I in pts with mCRC, MSI-H and non-MSI-H. Methods: Pts had ECOG PS 0–1, and intolerance/progression on ≥ 1 tx. MSI-H pts received N 3 mg/kg q2 wk (N3) or N 3 mg/kg + I 1 mg/kg q3 wk (N3+I1) x 4 doses followed by N3 until disease progression (PD) or other discontinuation. Initial evaluation of N+I at 3 doses was completed in non-MSI-H pts. Primary endpoint was investigator-reported ORR by RECIST 1.1; other endpoints were safety, OS, and PFS. Results: 33 (N3) and 26 (N3+I1) MSI-H pts, and 3 (N1+I1), 10 (N1+I3), and 10 (N3+I1) non-MSI-H pts were enrolled. 82% (N3) and 92% (N3+I1) of MSI-H and 100% of non-MSI-H pts had ≥ 2 prior regimens. 15% (N3) and 25% (N3+I1) of MSI-H pts had known BRAF V600E. 17 (52%; N3) and 19 (73%; N3+I1) MSI-H pts remain on tx. Efficacy results are shown in the Table. In MSI-H pts, tx-related adverse events (TRAEs) occurred in 26 (79%; N3) and 22 pts (85%; N3+I1); most common were diarrhea and fatigue (27% each; N3) and diarrhea (46%; N3+I1). Grade 3–4 TRAEs occurred in 7 (N3) and 8 pts (N3+I1). One pt on N3 had a Grade 5 TRAE (sudden death). In non-MSI-H pts median (95% CI) PFS was 1.4 mo (1.2–1.9; pooled N+I). Conclusions: N and N+I were well tolerated in most pts and demonstrated encouraging clinical activity and survival in MSI-H mCRC. This study is ongoing. Clinical trial information: NCT02060188.MSI-Ha efficacy. N3 (n = 33) N3+I1 (n = 26) ORR, n (%) 9 (27) 4 (15) CR 0 0 Confirmed PR 9 (27) 4 (15) SD 8 (24) 17 (65) PD 11 (33) 3 (12) Not determined/not reported 5 (15) 2 (8) Median duration of response (95% CI), mo NR (4.2–NE) NR (NE–NE) Median PFS (95% CI), mo 5.3 (1.4–NE) NR (NE–NE) 4-mo PFS rate,b % 55 80 Median OS (95% CI), mo 16.3 (8.3–NE) NR (NE–NE) 5-mo OS rate,c % 75 100 NR, not reached; NE, not estimable aBy local screen bPFS Kaplan-Meier plot estimate, N3 = 17/33 events, N3+I1 = 4/26 events cPFS Kaplan-Meier plot estimate, N3 = 11/33 events, N3+I1 = 0/26 events

No consensus exists regarding the best method of tonsillectomy. This report concerns two popular methods: 1. electrocautery excision and 2. dissection/snare followed by point coagulation of bleeding sites. To compare these methods, a prospective, randomized, single-blinded study was conducted in which 28 patients had one tonsil removed by dissection/snare and selective cautery of bleeders and the other removed by the electrocautery. Operative time and blood loss were compared. Patients rated the severity of their pain and blood loss postoperatively. Intraoperative bleeding was significantly less on the side of cautery excision, although the operative time was longer. At follow-up, pain was rated worse on the side of cautery excision.

8034 Background: The programmed death-1 receptor (PD-1) and its ligand (PD-L1) are key therapeutic targets in the reactivation of the immune response against cancer. Avelumab* (MSB0010718C) is a fully human anti-PD-L1 IgG1 antibody being investigated in clinical trials. We report safety and clinical activity in patients (pts) with advanced NSCLC progressing after platinum-based chemotherapy (NCT01772004). Methods: Pts were treated with avelumab at 10 mg/kg Q2W until progression, confirmed complete response (CR), or toxicity. A prespecified analysis of 184 pts with ≥ 3 months follow-up (range 3-13) was performed. Tumors were assessed every 6 weeks (w) (RECIST 1.1) and unconfirmed best overall response (BOR) was evaluated. Tumor PD-L1 expression was assessed by immunohistochemistry. Results: Median age was 65y (range 31-83) and ECOG PS was 0 (30%) or 1 (70%). Histology was adenocarcinoma (62%), squamous cell carcinoma (29%), or other (9%). Any grade drug-related treatment-emergent adverse events (TEAEs) occurred in 139 (75.5%) pts; the most common ( > 5%) were fatigue, nausea, infusion-related reactions (IRRs), chills, decreased appetite, and diarrhea. Drug-related grade ≥ 3 TEAEs occurred in 22 (12%) pts, including 4 IRRs. Drug-related deaths were reported (n = 3; radiation pneumonitis, acute respiratory failure, and disease progression). Objective responses (OR) were observed in 22 (12%) pts (95% CI: 7.6, 17.5; 1 CR, 21 partial responses; 18 were ongoing at data cutoff). BOR of stable disease was observed in 70 pts (38%). Median progression-free survival (PFS) was 11.6 w (95% CI: 8.4, 12.1) and the PFS rate at 24 w was 25.4% (95% CI: 18.3, 33.2). Tumors were PD-L1(+) in 86% of evaluable pts (1% cutoff). The ORR in PD-L1(+) pts (n = 118) was 14.4% and 10.0% in PD-L1(-) pts (n = 20). Median PFS in PD-L1(+) pts was 11.7 w vs 5.9 w in PD-L1(-) pts. Conclusions: In pts with previously treated NSCLC, avelumab was administered safely with a toxicity profile similar to other anti-PD-1/anti-PD-L1 agents. A trend of greater activity in pts with PD-L1(+) tumors was observed. A randomized phase 3 trial of avelumab in pts with advanced NSCLC is planned. *Proposed INN. Clinical trial information: NCT01772004.

The current accepted treatment for chronic frontal sinus disease unresponsive to medical management and endoscopic surgery is an external approach to either obliterate the sinus or restore communication to the nasal cavity. Here reported is an endoscopic approach for resection of the intranasal frontal sinus floor, a modification of a procedure first described by Lothrop in 1899. Eleven patients underwent this operation from April 1993 to December 1993. One complication, a cerebrospinal fluid leak treated successfully endoscopically, has occurred. Of the 7 patients followed up 3 months or longer after surgery, only 1 has developed symptoms of recurrent frontal sinusitis. On the basis of this limited preliminary experience, the endoscopic Lothrop procedure shows promise as an effective operation designed to establish a physiologic communication between the frontal sinus and the nasal cavity in selected patients who would otherwise be candidates for an external approach.