Clinical factors associated with shorter durable response, and patterns of acquired resistance to first-line pembrolizumab monotherapy in PD-L1-positive non-small-cell lung ... View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2021-04-01

AUTHORS

Kazutaka Hosoya, Daichi Fujimoto, Takeshi Morimoto, Toru Kumagai, Akihiro Tamiya, Yoshihiko Taniguchi, Toshihide Yokoyama, Tadashi Ishida, Hirotaka Matsumoto, Katsuya Hirano, Ryota Kominami, Keisuke Tomii, Hidekazu Suzuki, Tomonori Hirashima, Satoshi Tanaka, Junji Uchida, Mitsunori Morita, Masaki Kanazu, Masahide Mori, Kenji Nagata, Ikue Fukuda, Motohiro Tamiya

ABSTRACT

BackgroundDespite the wide-spread use of immune checkpoint inhibitors (ICIs) in cancer chemotherapy, reports on patients developing acquired resistance (AR) to ICI therapy are scarce. Therefore, we first investigated the characteristics associated with shorter durable responses of ICI treatment and revealed the clinical patterns of AR and prognosis of the patients involved.MethodsWe conducted a retrospective multi-center cohort study that included NSCLC patients with PD-L1 tumor proportion scores of ≥50% who received first-line pembrolizumab and showed response to the therapy. Among patients showing response, progression-free survival (PFS) was investigated based on different clinically relevant factors. AR was defined as disease progression after partial or complete response based on Response Evaluation Criteria in Solid Tumors. Among patients with AR, patterns of AR and post-progression survival (PPS) were investigated. Oligoprogression was defined as disease progression in up to 5 individual progressive lesions.ResultsAmong 174 patients who received first-line pembrolizumab, 88 showed response and were included in the study. Among these patients, 46 (52%) developed AR. Patients with old age, poor performance status (PS), at least 3 metastatic organs, or bone metastasis showed significantly shorter PFS. Among 46 patients with AR, 32 (70%) developed AR as oligoprogression and showed significantly longer PPS than those with non-oligoprogressive AR.ConclusionsPatients with old age, poor PS, at least 3 metastatic organs, or bone metastasis showed shorter durable responses to pembrolizumab monotherapy. Oligoprogressive AR was relatively common and associated with better prognosis. Further research is required to develop optimal approaches for the treatment of these patients. More... »

PAGES

346

Journal

TITLE

BMC Cancer

ISSUE

1

VOLUME

21

Author Affiliations

  • Department of Respiratory Medicine, Kobe City Medical Center General Hospital, 2-1-1 Minatojimaminamimachi, Chuo-ku, 650-0047, Kobe-shi, Hyogo, Japan
  • Internal Medicine III, Wakayama Medical University, 811-1, Kimiidera, Wakayama City, 641-8509, Wakayama, Japan
  • Department of Clinical Epidemiology, Hyogo College of Medicine, 1-1 Mukogawa, 663-8501, Nishinomiya, Hyogo, Japan
  • Department of Thoracic Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, 541-8567, Osaka, Japan
  • Department of Internal Medicine, National Hospital Organization Kinki-Chuo Chest Medical Center, 1180, Nagasone-cho, Kita-ku, Sakai-shi, 591-8555, Osaka, Japan
  • Department of Respiratory Medicine, Kurashiki Central Hospital, 1-1-1, Miwa, Kurashiki-shi, 710-8602, Okayama, Japan
  • Department of Respiratory Medicine, Hyogo Prefectural Amagasaki General Medical Center, 2-17-77, Higashi-Naniwa-Cho, 660-8550, Amagasaki-shi, Hyogo, Japan
  • Department of Respiratory Medicine, Himeji Medical Center, 68, Honmachi, 670-8520, Himeji-shi, Hyogo, Japan
  • Department of Thoracic Oncology, Osaka Habikino Medical Center, 3-7-1, Habikino, Habikino-shi, 583-8588, Osaka, Japan
  • Department of Respiratory Medicine, Osaka General Medical Center, 3-1-56, Bandai-Higashi, Sumiyoshi-ku, Osaka-shi, 558-8558, Osaka, Japan
  • Department of Respiratory Medicine, Kobe City Medical Center West Hospital, 2-4, Ichiban-cho, Nagata-ku, 653-0013, Kobe-shi, Hyogo, Japan
  • Department of Thoracic Oncology, National Hospital Organization Osaka Toneyama Medical Center, 5-1-1, Toneyama, Toyonaka-shi, 560-0045, Osaka, Japan
  • Department of Respiratory Medicine, Itami City Hospital, 1-100, Koyaike, 664-8540, Itami-shi, Hyogo, Japan
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/s12885-021-08048-4

    DOI

    http://dx.doi.org/10.1186/s12885-021-08048-4

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1136864407

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/33794809


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