Perioperative pembrolizumab in early-stage non-small cell lung cancer (NSCLC): safety, efficacy, and exploratory biomarker analysis
Background Our study was designed to determine the safety, efficacy, and immunological effects of perioperative pembrolizumab in early-stage NSCLC.Methods This is a single-arm phase II study of perioperative pembrolizumab in patients with untreated, clinical stage IB to IIIA NSCLC. Patients received...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2025-02-01
|
| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/13/2/e010395.full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832540460520833024 |
|---|---|
| author | Jeff Clarke Xiaofei Wang Thomas Stinchcombe Scott J Antonia Jeffrey Crawford Neal Ready Konstantin H Dragnev Lin Gu Cameron Wood James M Isaacs Liliana Lyniv Kent Weinhold Jacob M Kaufman Eziafa I Oduah Betty C Tong Dennis Wigle |
| author_facet | Jeff Clarke Xiaofei Wang Thomas Stinchcombe Scott J Antonia Jeffrey Crawford Neal Ready Konstantin H Dragnev Lin Gu Cameron Wood James M Isaacs Liliana Lyniv Kent Weinhold Jacob M Kaufman Eziafa I Oduah Betty C Tong Dennis Wigle |
| author_sort | Jeff Clarke |
| collection | DOAJ |
| description | Background Our study was designed to determine the safety, efficacy, and immunological effects of perioperative pembrolizumab in early-stage NSCLC.Methods This is a single-arm phase II study of perioperative pembrolizumab in patients with untreated, clinical stage IB to IIIA NSCLC. Patients received two doses of 200 mg pembrolizumab, surgery, standard adjuvant chemotherapy, followed by four doses adjuvant pembrolizumab. The primary objective of this study was to determine surgical feasibility rate, and secondary objectives are pathological response rate, treatment adverse events, efficacy data, and exploratory analysis of biomarkers.Results 30 patients initiated perioperative pembrolizumab, and 25 completed tumor resection. At median follow-up of 59 months after surgical resection, seven patients had disease progression, while six had died representing. A 5-year progression-free survival (PFS) from time of surgery was 72.0% (56.4%–91.9%) and overall survival (OS) from time of surgery was 75.8% (60.7%–94.7%). Major pathological response (MPR) was found in seven tumors (28%) including two complete responses (4%). Across all treated patients, four receiving neoadjuvant and four receiving adjuvant pembrolizumab experienced treatment-related adverse events of grade 3 or higher with no grade 5 events. Plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) levels increased across our patient cohort over time from baseline until postsurgery and remained elevated at the end of treatment. There was a significant difference between mean plasma PCSK9 levels for patients with MPR versus all other patients on study when checked postoperatively.Conclusions Perioperative pembrolizumab was safe and effective with promising MPR rate, PFS, and OS. |
| format | Article |
| id | doaj-art-60e5a4ef436f4acf917577af2440e287 |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-60e5a4ef436f4acf917577af2440e2872025-02-05T03:55:09ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262025-02-0113210.1136/jitc-2024-010395Perioperative pembrolizumab in early-stage non-small cell lung cancer (NSCLC): safety, efficacy, and exploratory biomarker analysisJeff Clarke0Xiaofei Wang1Thomas Stinchcombe2Scott J Antonia3Jeffrey Crawford4Neal Ready5Konstantin H Dragnev6Lin Gu7Cameron Wood8James M Isaacs9Liliana Lyniv10Kent Weinhold11Jacob M Kaufman12Eziafa I Oduah13Betty C Tong14Dennis Wigle15Division of Medical Oncology, Duke University Health System, Durham, North Carolina, USADuke Cancer Institute Biostatistics, Duke University School of Medicine, Durham, North Carolina, USADivision of Medical Oncology, Duke University Health System, Durham, North Carolina, USAMedical Oncology, Duke University Medical Center, Durham, North Carolina, USADivision of Medical Oncology, Duke University Health System, Durham, North Carolina, USAMedical Oncology, Duke University Medical Center, Durham, North Carolina, USADivision of Hematology-Oncology, Dartmouth-Hitchcock Norris Cotton Cancer Center, Lebanon, New Hampshire, USADuke Cancer Institute Biostatistics, Duke University School of Medicine, Durham, North Carolina, USAMedical Oncology, Bon Secours Richmond Health System, Kilmarnock, Virginia, USADivision of Hematology Oncology, Cleveland Clinic, Cleveland, Ohio, USADivision of Medical Oncology, Duke University Health System, Durham, North Carolina, USADepartment of Surgery, Duke University Health System, Durham, North Carolina, USADivision of Medical Oncology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USADivision of Medical Oncology, Duke University Health System, Durham, North Carolina, USADivision of Cardiovascular and Thoracic Surgery, Duke University Health System, Durham, North Carolina, USADepartment of Thoracic Surgery, Mayo Clinic, Rochester, Minnesota, USABackground Our study was designed to determine the safety, efficacy, and immunological effects of perioperative pembrolizumab in early-stage NSCLC.Methods This is a single-arm phase II study of perioperative pembrolizumab in patients with untreated, clinical stage IB to IIIA NSCLC. Patients received two doses of 200 mg pembrolizumab, surgery, standard adjuvant chemotherapy, followed by four doses adjuvant pembrolizumab. The primary objective of this study was to determine surgical feasibility rate, and secondary objectives are pathological response rate, treatment adverse events, efficacy data, and exploratory analysis of biomarkers.Results 30 patients initiated perioperative pembrolizumab, and 25 completed tumor resection. At median follow-up of 59 months after surgical resection, seven patients had disease progression, while six had died representing. A 5-year progression-free survival (PFS) from time of surgery was 72.0% (56.4%–91.9%) and overall survival (OS) from time of surgery was 75.8% (60.7%–94.7%). Major pathological response (MPR) was found in seven tumors (28%) including two complete responses (4%). Across all treated patients, four receiving neoadjuvant and four receiving adjuvant pembrolizumab experienced treatment-related adverse events of grade 3 or higher with no grade 5 events. Plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) levels increased across our patient cohort over time from baseline until postsurgery and remained elevated at the end of treatment. There was a significant difference between mean plasma PCSK9 levels for patients with MPR versus all other patients on study when checked postoperatively.Conclusions Perioperative pembrolizumab was safe and effective with promising MPR rate, PFS, and OS.https://jitc.bmj.com/content/13/2/e010395.full |
| spellingShingle | Jeff Clarke Xiaofei Wang Thomas Stinchcombe Scott J Antonia Jeffrey Crawford Neal Ready Konstantin H Dragnev Lin Gu Cameron Wood James M Isaacs Liliana Lyniv Kent Weinhold Jacob M Kaufman Eziafa I Oduah Betty C Tong Dennis Wigle Perioperative pembrolizumab in early-stage non-small cell lung cancer (NSCLC): safety, efficacy, and exploratory biomarker analysis Journal for ImmunoTherapy of Cancer |
| title | Perioperative pembrolizumab in early-stage non-small cell lung cancer (NSCLC): safety, efficacy, and exploratory biomarker analysis |
| title_full | Perioperative pembrolizumab in early-stage non-small cell lung cancer (NSCLC): safety, efficacy, and exploratory biomarker analysis |
| title_fullStr | Perioperative pembrolizumab in early-stage non-small cell lung cancer (NSCLC): safety, efficacy, and exploratory biomarker analysis |
| title_full_unstemmed | Perioperative pembrolizumab in early-stage non-small cell lung cancer (NSCLC): safety, efficacy, and exploratory biomarker analysis |
| title_short | Perioperative pembrolizumab in early-stage non-small cell lung cancer (NSCLC): safety, efficacy, and exploratory biomarker analysis |
| title_sort | perioperative pembrolizumab in early stage non small cell lung cancer nsclc safety efficacy and exploratory biomarker analysis |
| url | https://jitc.bmj.com/content/13/2/e010395.full |
| work_keys_str_mv | AT jeffclarke perioperativepembrolizumabinearlystagenonsmallcelllungcancernsclcsafetyefficacyandexploratorybiomarkeranalysis AT xiaofeiwang perioperativepembrolizumabinearlystagenonsmallcelllungcancernsclcsafetyefficacyandexploratorybiomarkeranalysis AT thomasstinchcombe perioperativepembrolizumabinearlystagenonsmallcelllungcancernsclcsafetyefficacyandexploratorybiomarkeranalysis AT scottjantonia perioperativepembrolizumabinearlystagenonsmallcelllungcancernsclcsafetyefficacyandexploratorybiomarkeranalysis AT jeffreycrawford perioperativepembrolizumabinearlystagenonsmallcelllungcancernsclcsafetyefficacyandexploratorybiomarkeranalysis AT nealready perioperativepembrolizumabinearlystagenonsmallcelllungcancernsclcsafetyefficacyandexploratorybiomarkeranalysis AT konstantinhdragnev perioperativepembrolizumabinearlystagenonsmallcelllungcancernsclcsafetyefficacyandexploratorybiomarkeranalysis AT lingu perioperativepembrolizumabinearlystagenonsmallcelllungcancernsclcsafetyefficacyandexploratorybiomarkeranalysis AT cameronwood perioperativepembrolizumabinearlystagenonsmallcelllungcancernsclcsafetyefficacyandexploratorybiomarkeranalysis AT jamesmisaacs perioperativepembrolizumabinearlystagenonsmallcelllungcancernsclcsafetyefficacyandexploratorybiomarkeranalysis AT lilianalyniv perioperativepembrolizumabinearlystagenonsmallcelllungcancernsclcsafetyefficacyandexploratorybiomarkeranalysis AT kentweinhold perioperativepembrolizumabinearlystagenonsmallcelllungcancernsclcsafetyefficacyandexploratorybiomarkeranalysis AT jacobmkaufman perioperativepembrolizumabinearlystagenonsmallcelllungcancernsclcsafetyefficacyandexploratorybiomarkeranalysis AT eziafaioduah perioperativepembrolizumabinearlystagenonsmallcelllungcancernsclcsafetyefficacyandexploratorybiomarkeranalysis AT bettyctong perioperativepembrolizumabinearlystagenonsmallcelllungcancernsclcsafetyefficacyandexploratorybiomarkeranalysis AT denniswigle perioperativepembrolizumabinearlystagenonsmallcelllungcancernsclcsafetyefficacyandexploratorybiomarkeranalysis |