A lack of association between BMI and chemoimmunotherapy efficacy in advanced non-small cell lung cancer: Secondary analysis of the IMpower150 and IMpower130 clinical trials
Abstract Background Multiple studies have indicated that patients with high body mass index (BMI) may have favourable survival outcomes following treatment with an immune checkpoint inhibitor (ICI). However, this evidence is limited by several factors, notably the minimal evidence from randomised co...
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BMC
2024-03-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-024-12132-w |
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| author | Lee X. Li Mark A. Socinski Ganessan Kichenadasse Christos S. Karapetis Adel Shahnam Ross A. McKinnon Andrew Rowland Ashley M. Hopkins Michael J. Sorich |
| author_facet | Lee X. Li Mark A. Socinski Ganessan Kichenadasse Christos S. Karapetis Adel Shahnam Ross A. McKinnon Andrew Rowland Ashley M. Hopkins Michael J. Sorich |
| author_sort | Lee X. Li |
| collection | DOAJ |
| description | Abstract Background Multiple studies have indicated that patients with high body mass index (BMI) may have favourable survival outcomes following treatment with an immune checkpoint inhibitor (ICI). However, this evidence is limited by several factors, notably the minimal evidence from randomised controlled trials (RCTs), the use of categorised BMI with inconsistent cut point definitions, and minimal investigation of contemporary combination ICI therapy. Moreover, whether overweight and obese patients gain a larger benefit from contemporary frontline chemoimmunotherapy in non-small cell lung cancer (NSCLC) is unclear. Methods This secondary analysis pooled individual patient data from the intention-to-treat population of the IMpower130 and IMpower150 RCTs comparing chemoimmunotherapy versus chemotherapy. Co-primary outcomes were overall survival (OS) and progression-free survival (PFS). The potentially non-linear relationship between BMI and chemoimmunotherapy treatment effect was evaluated using Multivariable Fractional Polynomial Interaction (MFPI). As a sensitivity analysis, chemoimmunotherapy treatment effect (chemoimmunotherapy versus chemotherapy) on survival was also estimated for each BMI subgroup defined by World Health Organisation classification. Exploratory analyses in the respective chemoimmunotherapy and chemotherapy cohort were undertaken to examine the survival outcomes among BMI subgroups. Results A total of 1282 patients were included. From the MFPI analysis, BMI was not significantly associated with chemoimmunotherapy treatment effect with respect to either OS (p = 0.71) or PFS (p = 0.35). This was supported by the sensitivity analyses that demonstrated no significant treatment effect improvement in OS/PFS among overweight or obese patients compared to normal weight patients (OS: normal BMI HR = 0.74 95% CI 0.59–0.93, overweight HR = 0.78 95% CI 0.61–1.01, obese HR = 0.84 95% CI 0.59–1.20). Exploratory analyses further highlighted that survival outcomes were not significantly different across BMI subgroups in either the chemoimmunotherapy therapy cohort (Median OS: normal BMI 19.9 months, overweight 17.9 months, and obese 19.5 months, p = 0.7) or the chemotherapy cohort (Median OS: normal 14.1 months, overweight 15.9 months, and obese 16.7 months, p = 0.7). Conclusion There was no association between high BMI (overweight or obese individuals) and enhanced chemoimmunotherapy treatment benefit in front-line treatment of advanced non-squamous NSCLC. This contrasts with previous publications that showed a superior treatment benefit in overweight and obese patients treated with immunotherapy given without chemotherapy. |
| first_indexed | 2024-04-24T16:17:24Z |
| format | Article |
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| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-04-24T16:17:24Z |
| publishDate | 2024-03-01 |
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| spelling | doaj.art-3c107a499ab540bd87f7273a410748e32024-03-31T11:23:09ZengBMCBMC Cancer1471-24072024-03-012411810.1186/s12885-024-12132-wA lack of association between BMI and chemoimmunotherapy efficacy in advanced non-small cell lung cancer: Secondary analysis of the IMpower150 and IMpower130 clinical trialsLee X. Li0Mark A. Socinski1Ganessan Kichenadasse2Christos S. Karapetis3Adel Shahnam4Ross A. McKinnon5Andrew Rowland6Ashley M. Hopkins7Michael J. Sorich8College of Medicine and Public Health, Flinders Medical Centre, Flinders UniversityAdventHealth Cancer InstituteCollege of Medicine and Public Health, Flinders Medical Centre, Flinders UniversityFlinders Health and Medical Research Institute, Flinders UniversityDepartment of Medical Oncology, Peter McCallum Cancer CentreCollege of Medicine and Public Health, Flinders Medical Centre, Flinders UniversityCollege of Medicine and Public Health, Flinders Medical Centre, Flinders UniversityCollege of Medicine and Public Health, Flinders Medical Centre, Flinders UniversityCollege of Medicine and Public Health, Flinders Medical Centre, Flinders UniversityAbstract Background Multiple studies have indicated that patients with high body mass index (BMI) may have favourable survival outcomes following treatment with an immune checkpoint inhibitor (ICI). However, this evidence is limited by several factors, notably the minimal evidence from randomised controlled trials (RCTs), the use of categorised BMI with inconsistent cut point definitions, and minimal investigation of contemporary combination ICI therapy. Moreover, whether overweight and obese patients gain a larger benefit from contemporary frontline chemoimmunotherapy in non-small cell lung cancer (NSCLC) is unclear. Methods This secondary analysis pooled individual patient data from the intention-to-treat population of the IMpower130 and IMpower150 RCTs comparing chemoimmunotherapy versus chemotherapy. Co-primary outcomes were overall survival (OS) and progression-free survival (PFS). The potentially non-linear relationship between BMI and chemoimmunotherapy treatment effect was evaluated using Multivariable Fractional Polynomial Interaction (MFPI). As a sensitivity analysis, chemoimmunotherapy treatment effect (chemoimmunotherapy versus chemotherapy) on survival was also estimated for each BMI subgroup defined by World Health Organisation classification. Exploratory analyses in the respective chemoimmunotherapy and chemotherapy cohort were undertaken to examine the survival outcomes among BMI subgroups. Results A total of 1282 patients were included. From the MFPI analysis, BMI was not significantly associated with chemoimmunotherapy treatment effect with respect to either OS (p = 0.71) or PFS (p = 0.35). This was supported by the sensitivity analyses that demonstrated no significant treatment effect improvement in OS/PFS among overweight or obese patients compared to normal weight patients (OS: normal BMI HR = 0.74 95% CI 0.59–0.93, overweight HR = 0.78 95% CI 0.61–1.01, obese HR = 0.84 95% CI 0.59–1.20). Exploratory analyses further highlighted that survival outcomes were not significantly different across BMI subgroups in either the chemoimmunotherapy therapy cohort (Median OS: normal BMI 19.9 months, overweight 17.9 months, and obese 19.5 months, p = 0.7) or the chemotherapy cohort (Median OS: normal 14.1 months, overweight 15.9 months, and obese 16.7 months, p = 0.7). Conclusion There was no association between high BMI (overweight or obese individuals) and enhanced chemoimmunotherapy treatment benefit in front-line treatment of advanced non-squamous NSCLC. This contrasts with previous publications that showed a superior treatment benefit in overweight and obese patients treated with immunotherapy given without chemotherapy.https://doi.org/10.1186/s12885-024-12132-wImmune checkpoint inhibitorChemoimmunotherapyBody mass indexNon-small-cell lung cancer |
| spellingShingle | Lee X. Li Mark A. Socinski Ganessan Kichenadasse Christos S. Karapetis Adel Shahnam Ross A. McKinnon Andrew Rowland Ashley M. Hopkins Michael J. Sorich A lack of association between BMI and chemoimmunotherapy efficacy in advanced non-small cell lung cancer: Secondary analysis of the IMpower150 and IMpower130 clinical trials BMC Cancer Immune checkpoint inhibitor Chemoimmunotherapy Body mass index Non-small-cell lung cancer |
| title | A lack of association between BMI and chemoimmunotherapy efficacy in advanced non-small cell lung cancer: Secondary analysis of the IMpower150 and IMpower130 clinical trials |
| title_full | A lack of association between BMI and chemoimmunotherapy efficacy in advanced non-small cell lung cancer: Secondary analysis of the IMpower150 and IMpower130 clinical trials |
| title_fullStr | A lack of association between BMI and chemoimmunotherapy efficacy in advanced non-small cell lung cancer: Secondary analysis of the IMpower150 and IMpower130 clinical trials |
| title_full_unstemmed | A lack of association between BMI and chemoimmunotherapy efficacy in advanced non-small cell lung cancer: Secondary analysis of the IMpower150 and IMpower130 clinical trials |
| title_short | A lack of association between BMI and chemoimmunotherapy efficacy in advanced non-small cell lung cancer: Secondary analysis of the IMpower150 and IMpower130 clinical trials |
| title_sort | lack of association between bmi and chemoimmunotherapy efficacy in advanced non small cell lung cancer secondary analysis of the impower150 and impower130 clinical trials |
| topic | Immune checkpoint inhibitor Chemoimmunotherapy Body mass index Non-small-cell lung cancer |
| url | https://doi.org/10.1186/s12885-024-12132-w |
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