Abstract 1292P
Background
Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of non-small cell lung cancer, occurring in <1% of all lung tumors. PSC is highly resistant to conventional cytotoxic chemotherapies and confers a poor prognosis. Two single-arm, multicenter phase-II trials were conducted to evaluate the efficacy and safety of PD-1 inhibitors in patients with PSC.
Methods
We enrolled patients who had previously untreated PSC with PD-L1 expression on ≥50% of tumor cells to pembrolizumab monotherapy (200 mg Q3W) (NCCH1703) and those with any level of PD-L1 expression who had progressed on ≥1 lines of chemotherapy to nivolumab monotherapy (3 mg/kg or 240 mg Q2W) (NCCH1603). The primary endpoint was the objective response rate (ORR) by a central review. The secondary endpoints were the investigator-assessed ORR, disease control rate (DCR), progression-free survival (PFS), overall survival, 6-month survival rate, and safety.
Results
From July 2017 to March 2020, 35 patients were enrolled (22 received pembrolizumab, and 13 received nivolumab). The NCCH1603 trial was terminated early because of poor accrual. The patients’ median age was 70 years; 80.0% were males. Pleomorphic carcinoma was the most frequently-diagnosed pathological subtype. The ORR and DCR rates were 68.2% (complete response [CR]/partial response [PR], 2/13; 95% confidence interval [CI], 45.1–86.1) and 81.8% (95% CI, 59.7–94.8) in the NCCH1703 trial and 30.8% (CR/PR, 1/3; 95% CI, 9.1–61.4) and 53.8% (95% CI, 25.1–80.8) in the NCCH1603 trial, respectively. The median PFS was 15.2 (95% CI, 4.3-NR) and 2.3 (95% CI, 0.9-NR) months in the NCCH1703 and NCCH1603 trials, respectively. In the NCCH1703 trial, 10 of the 15 patients who achieved PR or CR are ongoing PR and CR state at the analysis time. All respondents in the NCCH1603 trial continued treatment benefits. In both the trials, grade ≥3 treatment-related adverse events (N = 5; encephalitis, pneumonitis, adrenal insufficiency, diarrhea, and hyperkalemia) occurred in four patients (11.4%).
Conclusions
PD-1 inhibitors as monotherapy in both first and subsequent lines of treatment in patients with PSC showed promising antitumor activity, with an acceptable safety profile.
Clinical trial identification
UMIN000027629; UMIN000023433.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
R. Toyozawa: Financial Interests, Personal, Other, Honoraria: Chugai Pharmaceutical; Financial Interests, Personal, Other, Honoraria: Eli Lilly Japan; Financial Interests, Personal, Other, Honoraria: Nippon Boehringer Ingelheim; Financial Interests, Personal, Other, Honoraria: Novartis Pharma; Financial Interests, Personal, Other, Honoraria: Taiho Pharmaceutical; Financial Interests, Institutional, Principal Investigator: AbbVie; Financial Interests, Institutional, Principal Investigator: Amgen; Financial Interests, Institutional, Principal Investigator: Daiichi Sankyo; Financial Interests, Institutional, Principal Investigator: Eli Lilly Japan; Financial Interests, Institutional, Principal Investigator: Pfizer; Financial Interests, Institutional, Principal Investigator: Takeda Pharmaceutical. Y. Goto: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Chugai; Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: Guardant Health Inc.; Financial Interests, Personal, Advisory Board: Illumina; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical; Financial Interests, Personal, Advisory Board: Ono Pharmaceutical; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Board: Taiho; Financial Interests, Personal, Invited Speaker: Taiho; Financial Interests, Personal, Invited Speaker: Thermo Fischer; Non-Financial Interests, Institutional, Principal Investigator: AbbVie; Non-Financial Interests, Institutional, Principal Investigator: Bristol Myers Squibb; Non-Financial Interests, Personal and Institutional, Principal Investigator: Chugai; Non-Financial Interests, Institutional, Principal Investigator: Daiichi Sankyo; Non-Financial Interests, Institutional, Principal Investigator: Eli Lilly; Financial Interests, Personal and Institutional, Principal Investigator: Novartis; Financial Interests, Personal and Institutional, Principal Investigator: Pfizer; Non-Financial Interests, Institutional, Research Grant: Preferred Network. Y. Fujiwara: Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Ono Pharmaceutical; Financial Interests, Personal, Advisory Board: Otsuka Pharmaceutical; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Novartis. Y. Okuma: Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Boehringer Ingelheim; Financial Interests, Personal, Other, Honoraria: Chugai Pharmaceutical; Financial Interests, Personal, Other, Honoraria: Eli Lilly; Financial Interests, Personal, Other, Honoraria: Ono Pharmaceutical; Financial Interests, Personal, Other, Honoraria: Taiho Pharmaceutical; Financial Interests, Institutional, Research Grant: AbbVie; Financial Interests, Institutional, Research Grant: Chugai Pharmaceutical. T. Kurata: Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Eli Lilly; Financial Interests, Personal, Speaker’s Bureau: Chugai; Financial Interests, Personal, Speaker’s Bureau: Ono Pharmaceutical; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Boehringer Ingelheim; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Institutional, Principal Investigator: MSD; Financial Interests, Institutional, Principal Investigator: AstraZeneca; Financial Interests, Institutional, Principal Investigator: Ono Pharmaceutical; Financial Interests, Institutional, Principal Investigator: Takeda; Financial Interests, Institutional, Principal Investigator: Eli Lilly. T. Yokoyama: Financial Interests, Personal, Other, Honoraria: Chugai Pharmaceutical; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Institutional, Research Grant: Chugai Pharmaceutical; Financial Interests, Institutional, Research Grant: Delta-Fly Pharma; Financial Interests, Institutional, Research Grant: Takeda Pharmaceutical; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Eli Lilly. H. Nokihara: Financial Interests, Institutional, Research Grant: Ono Pharmaceutical; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Chugai Pharmaceutical; Financial Interests, Institutional, Research Grant: Regeneron; Financial Interests, Institutional, Research Grant: Takeda Pharmaceutical; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Chugai Pharmaceutical; Financial Interests, Personal, Speaker’s Bureau: Eli Lilly; Financial Interests, Personal, Speaker’s Bureau: Taiho Pharmaceutical; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Speaker’s Bureau: Boehringer Ingelheim; Financial Interests, Personal, Speaker’s Bureau: Novartis. T. Yokoi: Financial Interests, Personal, Other, Honoraria: Chugai; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: Ono Pharmaceutical; Financial Interests, Personal, Other, Honoraria: Boehringer Ingelheim; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Eli Lilly; Financial Interests, Personal, Other, Honoraria: MSD; Financial Interests, Personal, Other, Honoraria: Taiho Pharmaceutical; Financial Interests, Institutional, Research Grant: Ono Pharmaceutical. T. Yamaguchi: Financial Interests, Personal, Speaker’s Bureau: Ono Pharmaceutical; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: MSD. Y. Shiraishi: Financial Interests, Institutional, Funding: Chugai Pharmaceutical; Financial Interests, Institutional, Principal Investigator: Chugai Pharmaceutical; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Ono Pharmaceutical; Financial Interests, Personal, Other, Honoraria: Eli Lilly; Financial Interests, Personal, Other, Honoraria: Taiho Pharmaceutical. M. Takeda: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Ono Pharmaceutical; Financial Interests, Personal, Speaker’s Bureau: Nippon Boehringer Ingelheim; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb Company; Financial Interests, Personal, Speaker’s Bureau: Chugai Pharmaceutical; Financial Interests, Personal, Speaker’s Bureau: Novartis Pharma. T. Tokito: Financial Interests, Personal, Other, Honoraria: Chugai Pharmaceutical; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: MSD. A. Nakamura: Non-Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Non-Financial Interests, Personal, Speaker’s Bureau: MSD; Non-Financial Interests, Personal, Speaker’s Bureau: Chugai Pharmaceutical; Non-Financial Interests, Personal, Speaker’s Bureau: Taiho Pharmaceutical. Y. Hosomi: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Eli Lilly; Financial Interests, Personal, Speaker’s Bureau: Taiho Pharmaceutical; Financial Interests, Personal, Speaker’s Bureau: Chugai Pharmaceutical; Financial Interests, Personal, Speaker’s Bureau: Ono Pharmaceutical; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Kyowa Kirin. Y. Ohe: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Chugai; Financial Interests, Personal, Advisory Board: Ono Pharmaceutical; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Kyorin; Financial Interests, Personal, Advisory Board: Celltrion; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Nippon Kayaku; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: Ono; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Taiho; Financial Interests, Personal, Invited Speaker: Nippon Kayaku; Financial Interests, Personal, Invited Speaker: Kyowa Hakko Kirin; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Chugai; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Ono; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Kyorin; Financial Interests, Institutional, Research Grant: Dainippon- Sumitomo; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Taiho; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Ignyta; Financial Interests, Institutional, Research Grant: Takeda; Financial Interests, Institutional, Research Grant: Kissei; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Institutional, Research Grant: Loxo. All other authors have declared no conflicts of interest.