Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2023 Jul 3;6(7):e2322915.
doi: 10.1001/jamanetworkopen.2023.22915.

Concomitant Proton Pump Inhibitor Use With Pembrolizumab Monotherapy vs Immune Checkpoint Inhibitor Plus Chemotherapy in Patients With Non-Small Cell Lung Cancer

Hayato Kawachi  1 , Tadaaki Yamada  1 , Motohiro Tamiya  2 , Yoshiki Negi  3 , Yasuhiro Goto  4 , Akira Nakao  5 , Shinsuke Shiotsu  6 , Keiko Tanimura  7 , Takayuki Takeda  7 , Asuka Okada  8 , Taishi Harada  9 , Koji Date  10 , Yusuke Chihara  11 , Isao Hasegawa  12 , Nobuyo Tamiya  13 , Masaki Ishida  1 , Yuki Katayama  1 , Kenji Morimoto  1 , Masahiro Iwasaku  1 , Shinsaku Tokuda  1 , Takashi Kijima  3 , Koichi Takayama  1
Affiliations
Multicenter Study

Concomitant Proton Pump Inhibitor Use With Pembrolizumab Monotherapy vs Immune Checkpoint Inhibitor Plus Chemotherapy in Patients With Non-Small Cell Lung Cancer

Hayato Kawachi et al. JAMA Netw Open. .

Abstract

Importance: Immune checkpoint inhibitor (ICI) monotherapy with pembrolizumab and ICI plus chemotherapy have been approved as first-line treatments for non-small cell lung cancer (NSCLC) for patients with a programmed cell death ligand-1 (PD-L1) tumor proportion score (TPS) of 50% or more, but the choice between these 2 therapeutic options is unclear.

Objective: To clarify the association of a history of concurrent medication use with treatment outcomes for ICIs with or without chemotherapy in patients with NSCLC with a high PD-L1 TPS and to determine whether these clinical histories are biomarkers for appropriate treatment selection.

Design, setting, and participants: This retrospective, multicenter cohort study at 13 hospitals in Japan included patients with advanced NSCLC with a PD-L1 TPS of 50% or more who had received pembrolizumab ICI monotherapy or ICI plus chemotherapy as the initial treatment between March 2017 and December 2020. The median (IQR) follow-up duration was 18.5 (9.2-31.2) months. Data were analyzed from April 2022 through May 2023.

Exposure: ICI monotherapy with pembrolizumab or ICI plus chemotherapy as first-line treatment.

Main outcomes and measures: The primary analysis was the association of treatment outcomes with baseline patient characteristics, including concomitant drug history, after propensity score matching. Cox proportional hazard models were used to determine the associations of patient characteristics with survival outcomes. Logistic regression analysis was used to determine the association of concomitant medication history with treatment outcomes and other patient characteristics.

Results: A total of 425 patients with NSCLC were enrolled in the study including 271 patients (median [range] age, 72 [43-90] years; 215 [79%] men) who were treated with pembrolizumab monotherapy as the first-line treatment and 154 patients (median [range] age, 69 [36-86] years; 121 [79%] men) who were treated with ICI plus chemotherapy as the first-line treatment. In multivariable analysis, a history of proton pump inhibitor (PPI) use was independently associated with shorter progression-free survival (PFS) in the pembrolizumab monotherapy group (hazard ratio [HR], 1.38; 95% CI, 1.00-1.91; P = .048), but not in the ICI plus chemotherapy group. In patients with a PPI history, both the median (IQR) PFS (19.3 [9.0 to not reached] months vs 5.7 [2.4 to 15.2] months; HR, 0.38; 95% CI, 0.20-0.72; P = .002) and the median (IQR) overall survival (not reached [9.0 months to not reached) vs 18.4 [10.5 to 50.0] months; HR, 0.43; 95% CI, 0.20-0.92; P = .03) were significantly longer in the ICI plus chemotherapy group than in the pembrolizumab monotherapy group. In patients without a history of PPI use, both the median (IQR) PFS (18.8 months [6.6 months to not reached] vs 10.6 months [2.7 months to not reached]; HR, 0.81; 95% CI, 0.56-1.17; P = .26) and the median (IQR) overall survival (not reached [12.6 months to not reached] vs 29.9 [13.3 to 54.3] months, HR, 0.75; 95% CI, 0.48-1.18; P = .21) did not differ between groups.

Conclusions and relevance: This cohort study found that a history of PPI use could be an important clinical factor in treatment decision-making for patients with NSCLC with a PD-L1 TPS of 50% or more.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Kawachi reported receiving personal fees from Ono Pharmaceutical Co. Ltd; Chugai Pharmaceutical Co Ltd; AstraZeneca KK; Taiho Pharmaceutical Co Ltd; Eli Lilly Japan KK; and Merck, Sharp & Dohme KK, outside the submitted work. Dr Yamada reported receiving grants from Ono Pharmaceutical; Janssen; AstraZeneca; and Takeda Pharmaceutical; personal fees from Eli Lilly; and holding a pending patent for PCT/JP2018/038202 with Ono Pharmaceutical, outside the submitted work. Dr M. Tamiya reported receiving grants from Boehringer Ingelheim; Ono Pharmaceutical; Bristol-Myers Squibb; Merck, Sharp & Dohme; Chugai Pharmaceutical; Daiichi-Sankyo; Eisai; and Janssen; personal fees from Boehringer Ingelheim; Ono Pharmaceutical; Merck, Sharp & Dohme; Chugai Pharmaceutical; AstraZeneca; Taiho Pharmaceutical; Eli Lilly; Novartis; Pfizer; Asahi Kasei Pharmaceutical; Bayer; Amgen; Kyowa-Kirin; and Nippon Kayaku, outside the submitted work. Dr Kijima reported receiving personal fees for lectures from Chugai Pharmaceutical Co, Ltd; and Merck, Sharp & Dohme KK, outside the submitted work. Dr Takayama reported receiving grants from Chugai Pharmaceutical; Ono Pharmaceutical; personal fees from AstraZeneca; Chugai Pharmaceutical; Merck, Sharp & Dohme; Eli Lilly; Boehringer-Ingelheim; and Daiichi-Sankyo, outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Treatment Outcome Adjusted by Propensity Score Matching in All Patients
The figure shows Kaplan-Meier survival curves for progression-free survival (A) and overall survival (B) for patients receiving immune checkpoint inhibitor (ICI) monotherapy (pembrolizumab) and ICI plus chemotherapy (N = 262).
Figure 2.
Figure 2.. Treatment Outcome Adjusted by Propensity Scores According to History of Proton Pump Inhibitor (PPI) Use
The figure shows Kaplan-Meier survival curves for progression-free survival (A) and overall survival (B) in patients receiving immune checkpoint inhibitor (ICI) monotherapy (pembrolizumab) and ICI plus chemotherapy who had a history of PPI use (n = 68) and the progression-free survival (C) and overall survival (D) in patients receiving ICI monotherapy (pembrolizumab) and ICI plus chemotherapy who did not have a history of PPI use (n = 190).
See this image and copyright information in PMC

Comment in

References

    1. Borghaei H, Paz-Ares L, Horn L, et al. . Nivolumab versus docetaxel in advanced nonsquamous non–small-cell lung cancer. N Engl J Med. 2015;373(17):1627-1639. doi:10.1056/NEJMoa1507643 - DOI - PMC - PubMed
    1. Brahmer J, Reckamp KL, Baas P, et al. . Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015;373(2):123-135. doi:10.1056/NEJMoa1504627 - DOI - PMC - PubMed
    1. Rittmeyer A, Barlesi F, Waterkamp D, et al. ; OAK Study Group . Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet. 2017;389(10066):255-265. doi:10.1016/S0140-6736(16)32517-X - DOI - PMC - PubMed
    1. Reck M, Rodríguez-Abreu D, Robinson AG, et al. ; KEYNOTE-024 Investigators . Pembrolizumab versus chemotherapy for PD-L1–positive non–small-cell lung cancer. N Engl J Med. 2016;375(19):1823-1833. doi:10.1056/NEJMoa1606774 - DOI - PubMed
    1. Herbst RS, Giaccone G, de Marinis F, et al. . Atezolizumab for first-line treatment of PD-L1-selected patients with NSCLC. N Engl J Med. 2020;383(14):1328-1339. doi:10.1056/NEJMoa1917346 - DOI - PubMed

Publication types