Yu-Jung Kim1, Bhumsuk Keam2, Chan-Young Ock3, Sanghoon Song4, Miso Kim3, Se Hyun Kim1, Ki Hwan Kim5, Jin-Soo Kim5, Tae Min Kim6, Dong-Wan Kim6, Jong Seok Lee1, Dae Seog Heo6. 1. Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea. 2. Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea; Cancer Research Institute, Seoul National University, Seoul, Republic of Korea. Electronic address: bhumsuk@snu.ac.kr. 3. Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. 4. Theragen Etex Bioinstitute, NGS Genome Division, Suwon, Republic of Korea. 5. Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Republic of Korea. 6. Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea; Cancer Research Institute, Seoul National University, Seoul, Republic of Korea.
Abstract
OBJECTIVE: Patients with etoposide/platinum-refractory extensive disease (ED) small-cell lung cancer (SCLC) have a dismal prognosis. We aimed to evaluate the efficacy and safety of pembrolizumab and paclitaxel combination therapy in these patients. METHODS: In this multi-center, phase II study, ED-SCLC patients who showed progression after etoposide/platinum chemotherapy received paclitaxel 175 mg/m2 every 3 weeks for up to six cycles. Pembrolizumab 200 mg was added from the second cycle and continued until disease progression or unacceptable toxicity. The primary endpoint was the objective response rate (ORR) and the secondary endpoints were progression-free survival (PFS), overall survival (OS), safety, and biomarker analyses including programmed death-ligand 1 (PD-L1) expression, next-generation sequencing, and flow cytometric analysis of peripheral blood cells. RESULTS: Of the 26 patients enrolled, the confirmed ORR was 23.1% (95%CI: 6.9%-39.3%); complete response: 3.9%, confirmed partial response [PR]: 19.2%, stable disease: 57.7%, progressive disease: 7.7%, and not evaluable: 11.5%. Including 4 cases of unconfirmed PRs, 38.5% of patients were responding and the disease control rate was 80.7%. The median PFS and OS were 5.0 months (95% CI: 2.7-6.7) and 9.1 months (95% CI: 6.5-15.0), respectively. The grade 3 or 4 adverse events observed included febrile neutropenia (7.7%), neutropenia (7.7%), asthenia (7.7%), hyponatremia (7.7%), and type I diabetes (7.7%). Targeted gene sequencing identified no specific genetic alterations correlated with the treatment, except for theMET copy number gain (PFS 10.5 versus 3.4 months, p = 0.019). CONCLUSIONS: Pembrolizumab and paclitaxel combination therapy showed a moderate activity with acceptable toxicity in patients with refractory ED-SCLC.
OBJECTIVE:Patients with etoposide/platinum-refractory extensive disease (ED) small-cell lung cancer (SCLC) have a dismal prognosis. We aimed to evaluate the efficacy and safety of pembrolizumab and paclitaxel combination therapy in these patients. METHODS: In this multi-center, phase II study, ED-SCLCpatients who showed progression after etoposide/platinum chemotherapy received paclitaxel 175 mg/m2 every 3 weeks for up to six cycles. Pembrolizumab 200 mg was added from the second cycle and continued until disease progression or unacceptable toxicity. The primary endpoint was the objective response rate (ORR) and the secondary endpoints were progression-free survival (PFS), overall survival (OS), safety, and biomarker analyses including programmed death-ligand 1 (PD-L1) expression, next-generation sequencing, and flow cytometric analysis of peripheral blood cells. RESULTS: Of the 26 patients enrolled, the confirmed ORR was 23.1% (95%CI: 6.9%-39.3%); complete response: 3.9%, confirmed partial response [PR]: 19.2%, stable disease: 57.7%, progressive disease: 7.7%, and not evaluable: 11.5%. Including 4 cases of unconfirmed PRs, 38.5% of patients were responding and the disease control rate was 80.7%. The median PFS and OS were 5.0 months (95% CI: 2.7-6.7) and 9.1 months (95% CI: 6.5-15.0), respectively. The grade 3 or 4 adverse events observed included febrile neutropenia (7.7%), neutropenia (7.7%), asthenia (7.7%), hyponatremia (7.7%), and type I diabetes (7.7%). Targeted gene sequencing identified no specific genetic alterations correlated with the treatment, except for theMET copy number gain (PFS 10.5 versus 3.4 months, p = 0.019). CONCLUSIONS:Pembrolizumab and paclitaxel combination therapy showed a moderate activity with acceptable toxicity in patients with refractory ED-SCLC.
Authors: Alexander R Abbas; Marina Ruiz de Galarreta; Yinghui Guan; Andrew X Zhu; Shan Lu; Hartmut Koeppen; Wenjun Zhang; Chih-Hung Hsu; Aiwu Ruth He; Baek-Yeol Ryoo; Thomas Yau; Ahmed O Kaseb; Adam M Burgoyne; Farshid Dayyani; Jessica Spahn; Wendy Verret; Richard S Finn; Han Chong Toh; Amaia Lujambio; Yulei Wang Journal: Nat Med Date: 2022-06-23 Impact factor: 87.241
Authors: Mitchell S von Itzstein; Amrit S Gonugunta; Helen G Mayo; John D Minna; David E Gerber Journal: Cancer J Date: 2020 Nov/Dec Impact factor: 2.074