Pembrolizumab hybrid dosing is non-inferior to flat dosing in advanced non-small cell lung cancer: a real-world, retrospective bicenter cohort study
Background Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment but come with high costs. Alternative ICI dosing strategies could reduce costs without losing efficacy. However, clinical efficacy data are lacking.Methods In this retrospective cohort trial, consecutive patients wit...
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BMJ Publishing Group
2025-02-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/13/2/e010065.full |
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| author | Egbert F Smit Willemijn S M E Theelen Michiel M Smeenk Vincent van der Noort Jeroen M A Hendrikx Hanieh Abedian Kalkhoran |
| author_facet | Egbert F Smit Willemijn S M E Theelen Michiel M Smeenk Vincent van der Noort Jeroen M A Hendrikx Hanieh Abedian Kalkhoran |
| author_sort | Egbert F Smit |
| collection | DOAJ |
| description | Background Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment but come with high costs. Alternative ICI dosing strategies could reduce costs without losing efficacy. However, clinical efficacy data are lacking.Methods In this retrospective cohort trial, consecutive patients with advanced non-small cell lung cancer (NSCLC) who received ≥1 cycle pembrolizumab±chemotherapy at two tertiary institutions were included. Hybrid dosed patients received either 100, 150 or 200 mg pembrolizumab every 3 weeks or double every 6 weeks depending on their weight: <65 kg, 65–90 kg or >90 kg, respectively. Standard-of-care flat dosed patients received 200 mg every 3 weeks or 400 mg every 6 weeks. Overall survival (OS) and progression-free survival (PFS) were assessed by Kaplan-Meier estimation, compared by log-rank test and HRs were calculated with the Cox proportional hazards model in both unweighted and inverse probability of treatment weighted (IPTW) cohorts. Non-inferiority margin was set at an HR of 1.15.Results In total, 375 patients and 391 patients were included and median follow-up was 43.1 and 61.0 months in the hybrid and flat dose cohort, respectively. OS was non-inferior in the hybrid dose cohort compared with the flat dose cohort: median 17.7 months (95% CI 14.9 to 20.9) vs 11.8 months (95% CI 9.3 to 13.8, HR 0.76, 95% CI 0.65 to 0.90, p<0.0001 for non-inferiority). After correcting for confounders by IPTW, OS remained non-inferior (HR 0.76, 95% CI 0.63 to 0.91, p<0.0001 for non-inferiority). PFS in the hybrid cohort was also non-inferior to the flat dose cohort with a median of 6.4 months (95% CI 5.7 to 7.7) vs 4.6 months (95% CI 3.9 to 5.5, HR 0.82, 95% CI 0.70 to 0.96, p<0.0001 for non-inferiority). In total, 26.2% (or 52.5 mg per cycle, p<0.0001) pembrolizumab was saved in the hybrid dose cohort accounting to US$36 331.36 per patient.Conclusions In this retrospective analysis of a large cohort of advanced NSCLC patients treated with pembrolizumab±chemotherapy, OS of hybrid dosed patients was non-inferior to flat dosed patients. OS remained non-inferior after correcting for possible confounding factors. This hybrid regimen resulted in significant savings of pembrolizumab and costs. |
| format | Article |
| id | doaj-art-fd5cac0fe6194db1b122029f5638608d |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMJ Publishing Group |
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| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-fd5cac0fe6194db1b122029f5638608d2025-02-07T04:40:13ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262025-02-0113210.1136/jitc-2024-010065Pembrolizumab hybrid dosing is non-inferior to flat dosing in advanced non-small cell lung cancer: a real-world, retrospective bicenter cohort studyEgbert F Smit0Willemijn S M E Theelen1Michiel M Smeenk2Vincent van der Noort3Jeroen M A Hendrikx4Hanieh Abedian Kalkhoran5Department of Pulmonary Diseases, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam, The NetherlandsDepartment of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam, The NetherlandsDepartment of Biometrics, Netherlands Cancer Institute, Amsterdam, The NetherlandsDepartment of Pharmacy & Pharmacology, Netherlands Cancer Institute, Amsterdam, The NetherlandsDepartment of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The NetherlandsBackground Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment but come with high costs. Alternative ICI dosing strategies could reduce costs without losing efficacy. However, clinical efficacy data are lacking.Methods In this retrospective cohort trial, consecutive patients with advanced non-small cell lung cancer (NSCLC) who received ≥1 cycle pembrolizumab±chemotherapy at two tertiary institutions were included. Hybrid dosed patients received either 100, 150 or 200 mg pembrolizumab every 3 weeks or double every 6 weeks depending on their weight: <65 kg, 65–90 kg or >90 kg, respectively. Standard-of-care flat dosed patients received 200 mg every 3 weeks or 400 mg every 6 weeks. Overall survival (OS) and progression-free survival (PFS) were assessed by Kaplan-Meier estimation, compared by log-rank test and HRs were calculated with the Cox proportional hazards model in both unweighted and inverse probability of treatment weighted (IPTW) cohorts. Non-inferiority margin was set at an HR of 1.15.Results In total, 375 patients and 391 patients were included and median follow-up was 43.1 and 61.0 months in the hybrid and flat dose cohort, respectively. OS was non-inferior in the hybrid dose cohort compared with the flat dose cohort: median 17.7 months (95% CI 14.9 to 20.9) vs 11.8 months (95% CI 9.3 to 13.8, HR 0.76, 95% CI 0.65 to 0.90, p<0.0001 for non-inferiority). After correcting for confounders by IPTW, OS remained non-inferior (HR 0.76, 95% CI 0.63 to 0.91, p<0.0001 for non-inferiority). PFS in the hybrid cohort was also non-inferior to the flat dose cohort with a median of 6.4 months (95% CI 5.7 to 7.7) vs 4.6 months (95% CI 3.9 to 5.5, HR 0.82, 95% CI 0.70 to 0.96, p<0.0001 for non-inferiority). In total, 26.2% (or 52.5 mg per cycle, p<0.0001) pembrolizumab was saved in the hybrid dose cohort accounting to US$36 331.36 per patient.Conclusions In this retrospective analysis of a large cohort of advanced NSCLC patients treated with pembrolizumab±chemotherapy, OS of hybrid dosed patients was non-inferior to flat dosed patients. OS remained non-inferior after correcting for possible confounding factors. This hybrid regimen resulted in significant savings of pembrolizumab and costs.https://jitc.bmj.com/content/13/2/e010065.full |
| spellingShingle | Egbert F Smit Willemijn S M E Theelen Michiel M Smeenk Vincent van der Noort Jeroen M A Hendrikx Hanieh Abedian Kalkhoran Pembrolizumab hybrid dosing is non-inferior to flat dosing in advanced non-small cell lung cancer: a real-world, retrospective bicenter cohort study Journal for ImmunoTherapy of Cancer |
| title | Pembrolizumab hybrid dosing is non-inferior to flat dosing in advanced non-small cell lung cancer: a real-world, retrospective bicenter cohort study |
| title_full | Pembrolizumab hybrid dosing is non-inferior to flat dosing in advanced non-small cell lung cancer: a real-world, retrospective bicenter cohort study |
| title_fullStr | Pembrolizumab hybrid dosing is non-inferior to flat dosing in advanced non-small cell lung cancer: a real-world, retrospective bicenter cohort study |
| title_full_unstemmed | Pembrolizumab hybrid dosing is non-inferior to flat dosing in advanced non-small cell lung cancer: a real-world, retrospective bicenter cohort study |
| title_short | Pembrolizumab hybrid dosing is non-inferior to flat dosing in advanced non-small cell lung cancer: a real-world, retrospective bicenter cohort study |
| title_sort | pembrolizumab hybrid dosing is non inferior to flat dosing in advanced non small cell lung cancer a real world retrospective bicenter cohort study |
| url | https://jitc.bmj.com/content/13/2/e010065.full |
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