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Nivolumab ± ipilimumab in pts with advanced (adv)/metastatic chemotherapyrefractory (CTx-R) gastric (G), esophageal (E), or gastroesophageal junction (GEJ) cancer: CheckMate 032 study
Yelena Yuriy Janjigian, Patrick Alexander Ott, Emiliano Calvo, Joseph W. Kim, Paolo Antonio Ascierto, Padmanee Sharma, et al.
J Clin Oncol 35, 2017 (suppl; abstr 4014)
Editorial comment from Prof Lordick & Dr Smyth:
Checkmate 032 shows that the combination of two checkpoint inhibitors with different mechanisms of action (anti-PD1 plus anti-CTLA4: Nivolumab 1mg/kg and Ipilimumab 3mg/kg every three weeks) shows promise for the treatment of advanced and pretreated gastric cancers. Response rates for PD-L1 positive gastric cancers were reported to be as high as 40% for combination therapy in PD-L1 positive patients and survival rates after 18 months of treatment in patients with PD-L1 positive tumors were as high as 50%. Whether or not this combination will be established as a chemotherapy free option in the treatment algorithm of gastric cancer depends on the results of ongoing randomized controlled trials.
In the phase 3 ONO-12 study, 3rd- or later-line nivolumab (N) monotherapy prolonged OS vs placebo in Asian pts with adv G/GEJ cancer (median OS, 5.3 vs 4.1 mo; HR, 0.63; P , 0.0001; ASCO-GI 2017, Kang YK et al. J Clin Oncol. 2017;35 (suppl 4S) [abstract 2]). The phase 1/2 CheckMate 032 study showed favorable clinical activity of N 6 ipilimumab (I) in Western pts with adv CTx-R G/E/GEJ cancer (NCT01928394). We report updated long-term follow-up data of G/E/GEJ pts in CheckMate 032.
Pts received N 3 mg/kg Q2W (N3), N 1 mg/kg + I 3 mg/kg Q3W (N1+I3), or N 3 mg/kg + I 1 mg/kg Q3W (N3+I1). Primary endpoint was ORR. Secondary endpoints included DOR, OS, PFS, and safety. Efficacy in pts by PD-L1 status was assessed.
160 heavily pretreated pts (79% had$ 2 prior Tx) were enrolled (N3, n = 59; N1+I3, n = 49; N3+I1, n = 52); 24% had PD-L1+ ($1%) tumors. ORR was 12% in N3, 24% in N1+I3, and 8% in N3+I1. In pts with PD-L1$ 1%, ORR was 19%(3/16) in N3, 40%(4/10) in N1+I3, and 23% (3/13) in N3 +I1; in pts with PD-L1 , 1%, ORR was 12% (3/26), 22% (7/32), and 0% (0/30), respectively. Median DOR was 7.1 mo in N3, 7.9 mo in N1+I3, andNA in N3+I1. OS in all pts and in pts with PD-L1$1% is in the Table. Grade 3–4 treatment-related AEs reported in$10% of pts in any treatment arm were diarrhea (N3, 2%; N1+I3, 14%; N3+I1, 2%), ALT increased (N3, 3%; N1+I3, 14%; N3+I1, 4%), and AST increased (N3, 5%; N1+I3, 10%; N3+I1, 2%).
N 6 I led to durable responses and long-term OS in heavily pretreated Western pts with adv G/E/GEJ cancer, which is consistent with the clinical activity observed in Asian pts in the ONO-12 study. Safety was consistent with prior reports. These data support ongoing investigation of N 6 I in pts with adv G/E/GEJ cancer. Clinical trial information: NCT01928394.
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