Reporting on patient's body mass index (BMI) in recent clinical trials for patients with breast cancer: a systematic review.
Body mass index (BMI)
Breast cancer
Clinical drug trials
Dosing
Obesity
Treatment efficacy
Journal
Breast cancer research : BCR
ISSN: 1465-542X
Titre abrégé: Breast Cancer Res
Pays: England
ID NLM: 100927353
Informations de publication
Date de publication:
22 May 2024
22 May 2024
Historique:
received:
27
11
2023
accepted:
30
04
2024
medline:
23
5
2024
pubmed:
23
5
2024
entrez:
22
5
2024
Statut:
epublish
Résumé
The proportion of patients with breast cancer and obesity is increasing. While the therapeutic landscape of breast cancer has been expanding, we lack knowledge about the potential differential efficacy of most drugs according to the body mass index (BMI). Here, we conducted a systematic review on recent clinical drug trials to document the dosing regimen of recent drugs, the reporting of BMI and the possible exclusion of patients according to BMI, other adiposity measurements and/or diabetes (leading comorbidity of obesity). We further explored whether treatment efficacy was evaluated according to BMI. A search of Pubmed and ClinicalTrials.gov was performed to identify phase I-IV trials investigating novel systemic breast cancer treatments. Dosing regimens and exclusion based on BMI, adiposity measurements or diabetes, documentation of BMI and subgroup analyses according to BMI were assessed. 495 trials evaluating 26 different drugs were included. Most of the drugs (21/26, 81%) were given in a fixed dose independent of patient weight. BMI was an exclusion criterion in 3 out of 495 trials. Patients with diabetes, the leading comorbidity of obesity, were excluded in 67/495 trials (13.5%). Distribution of patients according to BMI was mentioned in 8% of the manuscripts, subgroup analysis was performed in 2 trials. No other measures of adiposity/body composition were mentioned in any of the trials. Retrospective analyses on the impact of BMI were performed in 6 trials. Patient adiposity is hardly considered as most novel drug treatments are given in a fixed dose. BMI is generally not reported in recent trials and few secondary analyses are performed. Given the prevalence of patients with obesity and the impact obesity can have on pharmacokinetics and cancer biology, more attention should be given by investigators and study sponsors to reporting patient's BMI and evaluating its impact on treatment efficacy and toxicity.
Sections du résumé
BACKGROUND
BACKGROUND
The proportion of patients with breast cancer and obesity is increasing. While the therapeutic landscape of breast cancer has been expanding, we lack knowledge about the potential differential efficacy of most drugs according to the body mass index (BMI). Here, we conducted a systematic review on recent clinical drug trials to document the dosing regimen of recent drugs, the reporting of BMI and the possible exclusion of patients according to BMI, other adiposity measurements and/or diabetes (leading comorbidity of obesity). We further explored whether treatment efficacy was evaluated according to BMI.
METHODS
METHODS
A search of Pubmed and ClinicalTrials.gov was performed to identify phase I-IV trials investigating novel systemic breast cancer treatments. Dosing regimens and exclusion based on BMI, adiposity measurements or diabetes, documentation of BMI and subgroup analyses according to BMI were assessed.
RESULTS
RESULTS
495 trials evaluating 26 different drugs were included. Most of the drugs (21/26, 81%) were given in a fixed dose independent of patient weight. BMI was an exclusion criterion in 3 out of 495 trials. Patients with diabetes, the leading comorbidity of obesity, were excluded in 67/495 trials (13.5%). Distribution of patients according to BMI was mentioned in 8% of the manuscripts, subgroup analysis was performed in 2 trials. No other measures of adiposity/body composition were mentioned in any of the trials. Retrospective analyses on the impact of BMI were performed in 6 trials.
CONCLUSIONS
CONCLUSIONS
Patient adiposity is hardly considered as most novel drug treatments are given in a fixed dose. BMI is generally not reported in recent trials and few secondary analyses are performed. Given the prevalence of patients with obesity and the impact obesity can have on pharmacokinetics and cancer biology, more attention should be given by investigators and study sponsors to reporting patient's BMI and evaluating its impact on treatment efficacy and toxicity.
Identifiants
pubmed: 38778365
doi: 10.1186/s13058-024-01832-7
pii: 10.1186/s13058-024-01832-7
doi:
Substances chimiques
Antineoplastic Agents
0
Types de publication
Systematic Review
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
81Subventions
Organisme : European Research Council (ERC)
ID : FAT-BC 101003153
Organisme : European Research Council (ERC)
ID : FAT-BC 101003153
Organisme : European Research Council (ERC)
ID : FAT-BC 101003153
Informations de copyright
© 2024. The Author(s).
Références
World health statistics 2022: monitoring health for the SDGs, sustainable development goals. Geneva: World Health Organization; 2022. Licence: CC BY-NC-SA 3.0 IGO.
Lohmann AE, et al. Association of obesity with breast cancer outcome in relation to cancer subtypes: a meta-analysis. J Natl Cancer Inst. 2021;113:1465–75.
pubmed: 33620467
pmcid: 8562970
doi: 10.1093/jnci/djab023
Protani M, Coory M, Martin JH, Protani M, Martin JH. Effect of obesity on survival of women with breast cancer: systematic review and meta-analysis. Breast Cancer Res Treat. 2010;123:627–35.
pubmed: 20571870
doi: 10.1007/s10549-010-0990-0
Goodwin PJ, Stambolic V. Impact of the obesity epidemic on cancer. Annu Rev Med. 2015;66:281–96.
pubmed: 25423596
doi: 10.1146/annurev-med-051613-012328
Biganzoli E, et al. Recurrence dynamics of breast cancer according to baseline body mass index. Eur J Cancer. 2017;87:10–20.
pubmed: 29096156
doi: 10.1016/j.ejca.2017.10.007
Pai MP. Drug dosing based on weight and body surface area: mathematical assumptions and limitations in obese adults. Pharmacother J Human Pharmacol Drug Ther. 2012;32:856–68.
doi: 10.1002/j.1875-9114.2012.01108.x
Hoge RHL, et al. Lean body mass and total body weight versus body surface area as a determinant of docetaxel pharmacokinetics and toxicity. Ther Drug Monit. 2022;44:755–61.
pubmed: 36006609
doi: 10.1097/FTD.0000000000001029
Miller AA. Body surface area in dosing anticancer agents: scratch the surface! J Natl Cancer Inst. 2002;94:1822–31.
pubmed: 12488468
doi: 10.1093/jnci/94.24.1822
Redlarski G, Palkowski A, Krawczuk M. Body surface area formulae: an alarming ambiguity. Sci Rep. 2016;6:1–8.
doi: 10.1038/srep27966
Zhang T, Krekels EHJ, Smit C, Knibbe CAJ. Drug pharmacokinetics in the obese population: challenging common assumptions on predictors of obesity-related parameter changes. Expert Opin Drug Metab Toxicol. 2022;18:657–74.
pubmed: 36217846
doi: 10.1080/17425255.2022.2132931
Barras M, Legg A. Drug dosing in obese adults. Aust Prescr. 2017;40:189.
pubmed: 29109603
pmcid: 5662437
doi: 10.18773/austprescr.2017.053
Hanley MJ, Abernethy DR, Greenblatt DJ. Effect of obesity on the pharmacokinetics of drugs in humans. Clin Pharmacokinet. 2010;49:71–87.
pubmed: 20067334
doi: 10.2165/11318100-000000000-00000
Cheymol G. Effects of obesity on pharmacokinetics implications for drug therapy. Clin Pharmacokinet. 2000;39:215–31.
pubmed: 11020136
doi: 10.2165/00003088-200039030-00004
Talevi A, Bellera CL. Drug absorption. In: ADME processes in pharmaceutical sciences: dosage, design, and pharmacotherapy success, pp 11–96 (2023). https://doi.org/10.1007/978-3-319-99593-9_2
Abernethy DR, Greenblatt DJ, Divoll M, Shader RI. Prolonged accumulation of diazepam in obesity. J Clin Pharmacol. 1983;23:369–76.
pubmed: 6415130
doi: 10.1002/j.1552-4604.1983.tb02750.x
Kim YS, Nam YS, Kim DI. Evaluating the effectiveness of gluteal intramuscular injection sites: a cadaveric study. Anat Cell Biol. 2022;55:48.
pubmed: 35115416
pmcid: 8968225
doi: 10.5115/acb.21.223
Wei J, Zhang Y, Li Z, Li X, Zhao C. Docetaxel population pharmacokinetic modelling and simulation in Chinese cancer patients. Ann Transl Med. 2022;10:705–705.
pubmed: 35845493
pmcid: 9279759
doi: 10.21037/atm-22-2619
Desmedt C, et al. Differential benefit of adjuvant docetaxel-based chemotherapy in patients with early breast cancer according to baseline body mass index. J Clin Oncol. 2020;38:2883–91.
pubmed: 32614702
doi: 10.1200/JCO.19.01771
Goldstein MJ, Peters M, Weber BL, Davis CB. Optimizing the therapeutic window of targeted drugs in oncology: potency-guided first-in-human studies. Clin Transl Sci. 2021;14:536.
pubmed: 33048459
doi: 10.1111/cts.12902
Le Louedec F, et al. Cancer immunotherapy dosing: a pharmacokinetic/pharmacodynamic perspective. Vaccines (Basel). 2020;8:1–23.
Hendrikx JJMA, et al. Fixed dosing of monoclonal antibodies in oncology. Oncologist. 2017;22:1212–21.
pubmed: 28754722
pmcid: 5634778
doi: 10.1634/theoncologist.2017-0167
Ewertz M, et al. Effect of obesity on prognosis after early-stage breast cancer. J Clin Oncol. 2011;29:25–31.
pubmed: 21115856
doi: 10.1200/JCO.2010.29.7614
Barone I, et al. Obesity and endocrine therapy resistance in breast cancer: mechanistic insights and perspectives. Obes Rev. 2022;23:e13358.
pubmed: 34559450
doi: 10.1111/obr.13358
Bougaret L, et al. Adipocyte/breast cancer cell crosstalk in obesity interferes with the anti-proliferative efficacy of tamoxifen. PLoS ONE. 2018;13:e0191571.
pubmed: 29389973
pmcid: 5794086
doi: 10.1371/journal.pone.0191571
Sestak I, et al. Effect of body mass index on recurrences in tamoxifen and anastrozole treated women: an exploratory analysis from the ATAC trial. J Clin Oncol. 2010;28:3411–5.
pubmed: 20547990
doi: 10.1200/JCO.2009.27.2021
Isnaldi E, et al. The association between adiposity and anti-proliferative response to neoadjuvant endocrine therapy with letrozole in post-menopausal patients with estrogen receptor positive breast cancer. NPJ Breast Cancer. 2022;8:1–10.
doi: 10.1038/s41523-022-00453-7
Yoo SK, Chowell D, Valero C, Morris LGT, Chan TA. Outcomes among patients with or without obesity and with cancer following treatment with immune checkpoint blockade. JAMA Netw Open. 2022;5:e220448–e220448.
pubmed: 35226089
pmcid: 8886536
doi: 10.1001/jamanetworkopen.2022.0448
Quail DF, Dannenberg AJ. The obese adipose tissue microenvironment in cancer development and progression. Nat Rev Endocrinol. 2018;15:139–54.
doi: 10.1038/s41574-018-0126-x
Iyengar NM, Hudis CA, Dannenberg AJ. Obesity and cancer: local and systemic mechanisms. Annu Rev Med. 2015;66:297–309.
pubmed: 25587653
doi: 10.1146/annurev-med-050913-022228
Nguyen HL, et al. Obesity-associated changes in molecular biology of primary breast cancer. Nat Commun. 2023;14:1–17.
doi: 10.1038/s41467-023-39996-z
GBD 2015 Obesity Collaborators. Health effects of overweight and obesity in 195 countries over 25 years. N Engl J Med. 2017; 377:13–27.
Chatterjee S, Khunti K, Davies MJ. Type 2 diabetes. The Lancet. 2017;389:2239–51.
doi: 10.1016/S0140-6736(17)30058-2
Elliott MJ, Cescon DW. Development of novel agents for the treatment of early estrogen receptor positive breast cancer. Breast Off J Eur Soc Mastol. 2022;62:S34.
Nagayama A, Vidula N, Bardia A. Novel therapies for metastatic triple-negative breast cancer: spotlight on immunotherapy and antibody-drug conjugates. Oncology (Williston Park). 2021;35:249–54.
pubmed: 33983696
doi: 10.46883/ONC.2021.3505.0249
Martin M, López-Tarruella S. Emerging therapeutic options for HER2-positive breast cancer. Am Soc Clin Oncol Educ Book. 2016;35:e64–70.
pubmed: 27249772
doi: 10.1200/EDBK_159167
Yu Y, et al. Palbociclib (PD-0332991) pharmacokinetics in subjects with impaired renal function. Cancer Chemother Pharmacol. 2020;86:701–10.
pubmed: 33037918
doi: 10.1007/s00280-020-04163-4
Emens LA, et al. Long-term clinical outcomes and biomarker analyses of atezolizumab therapy for patients with metastatic triple-negative breast cancer: a phase 1 study. JAMA Oncol. 2019;5:74–82.
pubmed: 30242306
doi: 10.1001/jamaoncol.2018.4224
Herbst RS, et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014;515:563–7.
pubmed: 25428504
pmcid: 4836193
doi: 10.1038/nature14011
Nanda R, et al. Pembrolizumab in patients with advanced triple-negative breast cancer: phase Ib KEYNOTE-012 study. J Clin Oncol. 2016;34:2460–7.
pubmed: 27138582
pmcid: 6816000
doi: 10.1200/JCO.2015.64.8931
Weiss GJ, et al. A phase Ib study of pembrolizumab plus chemotherapy in patients with advanced cancer (PembroPlus). Br J Cancer. 2017;117:33–40.
pubmed: 28588322
pmcid: 5520208
doi: 10.1038/bjc.2017.145
Rugo HS, et al. Safety and antitumor activity of pembrolizumab in patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer. Clin Cancer Res. 2018;24:2804–11.
pubmed: 29559561
doi: 10.1158/1078-0432.CCR-17-3452
Mansoor A, Mahabadi N. Volume of distribution. Transl Clin Pharmacol. 2023;24:74–7.
Marra A, Curigliano G. Are all cyclin-dependent kinases 4/6 inhibitors created equal? NPJ Breast Cancer. 2019;5:27.
pubmed: 31482107
pmcid: 6715721
doi: 10.1038/s41523-019-0121-y
Samant TS, Yang S, Miller M, Ji Y. Pharmacokinetics of ribociclib in subjects with hepatic impairment. J Clin Pharmacol. 2021;61:1001–9.
pubmed: 33555033
doi: 10.1002/jcph.1825
Miller C, et al. Pharmacokinetics of the Akt Serine/threonine protein kinase inhibitor, capivasertib, administered to healthy volunteers in the presence and absence of the CYP3A4 inhibitor itraconazole. Clin Pharmacol Drug Dev. 2023;12:856–62.
pubmed: 37449963
doi: 10.1002/cpdd.1307
Yam C, et al. Efficacy and safety of the combination of metformin, everolimus and exemestane in overweight and obese postmenopausal patients with metastatic, hormone receptor-positive, HER2-negative breast cancer: a phase II study. Invest New Drugs. 2019;37:345–51.
pubmed: 30610588
doi: 10.1007/s10637-018-0700-z
Ershow AG. Personalized medicine for diabetes: environmental influences on development of Type 2 diabetes and obesity: challenges in personalizing prevention and management. J Diabetes Sci Technol. 2009;3:727.
pubmed: 20144320
pmcid: 2769972
doi: 10.1177/193229680900300418
Barnes AS, Coulter SA. The epidemic of obesity and diabetes: trends and treatments. Tex Heart Inst J. 2011;38:142.
pubmed: 21494521
pmcid: 3066828
Waks AG, et al. Phase Ib study of pembrolizumab in combination with trastuzumab emtansine for metastatic HER2-positive breast cancer. J Immunother Cancer. 2022;10:e005119.
pubmed: 36252998
pmcid: 9577940
doi: 10.1136/jitc-2022-005119
Yam C, et al. A phase II study of neoadjuvant atezolizumab and nab-paclitaxel in patients with anthracycline-resistant early-stage triple-negative breast cancer. Breast Cancer Res Treat. 2023;199:457–69.
pubmed: 37061619
doi: 10.1007/s10549-023-06929-9
Yuan Y, et al. Phase I trial of ipatasertib plus carboplatin, carboplatin/paclitaxel, or capecitabine and atezolizumab in metastatic triple-negative breast cancer. Oncologist. 2023;28:e498–507.
pubmed: 37023705
pmcid: 10322142
doi: 10.1093/oncolo/oyad026
Gianni L, et al. Neoadjuvant treatment with trastuzumab and pertuzumab plus palbociclib and fulvestrant in HER2-positive, ER-positive breast cancer (NA-PHER2): an exploratory, open-label, phase 2 study. Lancet Oncol. 2018;19:249–56.
pubmed: 29326029
doi: 10.1016/S1470-2045(18)30001-9
Yan M, et al. Dalpiciclib and pyrotinib in women with HER2-positive advanced breast cancer: a single-arm phase II trial. Nat Commun. 2023;14:6272.
pubmed: 37805496
pmcid: 10560297
doi: 10.1038/s41467-023-41955-7
Yonemori K, et al. A phase I/II trial of olaparib tablet in combination with eribulin in Japanese patients with advanced or metastatic triple-negative breast cancer previously treated with anthracyclines and taxanes. Eur J Cancer. 2019;109:84–91.
pubmed: 30703739
doi: 10.1016/j.ejca.2018.11.014
Li Q, et al. Safety, efficacy, and biomarker analysis of pyrotinib in combination with capecitabine in HER2-positive metastatic breast cancer patients: a phase I clinical trial. Clin Cancer Res. 2019;25:5212–20.
pubmed: 31138588
doi: 10.1158/1078-0432.CCR-18-4173
Hu ZY, et al. Pyrotinib in combination with letrozole for hormone receptor-positive, human epidermal growth factor receptor 2-positive metastatic breast cancer (PLEHERM): a multicenter, single-arm, phase II trial. BMC Med. 2023;21:226.
pubmed: 37365596
pmcid: 10294469
doi: 10.1186/s12916-023-02943-2
Cao J, et al. Pyrotinib plus capecitabine for trastuzumab-resistant, HER2-positive advanced breast cancer (PICTURE): a single-arm, multicenter phase 2 trial. BMC Med. 2023;21:1–10.
doi: 10.1186/s12916-023-02999-0
Savas P, et al. Alpelisib monotherapy for PI3K-altered, pretreated advanced breast cancer: a phase II study. Cancer Discov. 2022;12:2058–73.
pubmed: 35771551
doi: 10.1158/2159-8290.CD-21-1696
Jhaveri K, et al. A phase I study of alpelisib in combination with trastuzumab and LJM716 in patients with PIK3CA-mutated HER2-positive metastatic breast cancer. Clin Cancer Res. 2021;27:3867.
pubmed: 33947692
pmcid: 8282678
doi: 10.1158/1078-0432.CCR-21-0047
McRee AJ, et al. A phase I trial of the PI3K inhibitor buparlisib combined with capecitabine in patients with metastatic breast cancer. Clin Breast Cancer. 2018;18:289.
pubmed: 29153866
doi: 10.1016/j.clbc.2017.10.014
Welt A, et al. Buparlisib in combination with tamoxifen in pretreated patients with hormone receptor-positive, HER2-negative advanced breast cancer molecularly stratified for PIK3CA mutations and loss of PTEN expression. Cancer Med. 2020;9:4527–39.
pubmed: 32352244
pmcid: 7333856
doi: 10.1002/cam4.3092
Garrido-Castro AC, et al. Phase 2 study of buparlisib (BKM120), a pan-class I PI3K inhibitor, in patients with metastatic triple-negative breast cancer. Breast Cancer Res. 2020;22:1–13.
doi: 10.1186/s13058-020-01354-y
Infante JR, et al. A phase I dose-escalation study of Selumetinib in combination with Erlotinib or Temsirolimus in patients with advanced solid tumors. Invest New Drugs. 2017;35:576.
pubmed: 28424891
pmcid: 5613062
doi: 10.1007/s10637-017-0459-7
Schmid P, et al. Fulvestrant plus vistusertib vs fulvestrant plus everolimus vs fulvestrant alone for women with hormone receptor-positive metastatic breast cancer: the MANTA Phase 2 Randomized clinical trial. JAMA Oncol. 2019;5:1556.
pubmed: 31465093
pmcid: 6865233
doi: 10.1001/jamaoncol.2019.2526
Park IH, et al. Phase I/II clinical trial of everolimus combined with gemcitabine/cisplatin for metastatic triple-negative breast cancer. J Cancer. 2018;9:1145.
pubmed: 29675095
pmcid: 5907662
doi: 10.7150/jca.24035
Baselga J, et al. Phase II randomized study of neoadjuvant everolimus plus letrozole compared with placebo plus letrozole in patients with estrogen receptor-positive breast cancer. J Clin Oncol. 2009;27:2630–7.
pubmed: 19380449
doi: 10.1200/JCO.2008.18.8391
Gonzalez-Angulo AM, et al. Biologic markers in axillary node-negative breast cancer: differential expression in invasive ductal carcinoma versus invasive lobular carcinoma. Clin Breast Cancer. 2006;7:396–400.
pubmed: 17239264
doi: 10.3816/CBC.2006.n.056
Clark AS, et al. Combination paclitaxel and palbociclib: results of a phase I trial in advanced breast cancer. Clin Cancer Res. 2019;25:2072–9.
pubmed: 30635336
doi: 10.1158/1078-0432.CCR-18-0790
Curigliano G, et al. Alpelisib in combination with everolimus ± exemestane in solid tumours: phase Ib randomised, open-label, multicentre study. Eur J Cancer. 2021;151:49–62.
pubmed: 33964572
doi: 10.1016/j.ejca.2021.03.042
Bardia A, et al. Phase Ib study of combination therapy with MEK Inhibitor binimetinib and phosphatidylinositol 3-kinase inhibitor buparlisib in patients with advanced solid tumors with RAS/RAF alterations. Oncologist. 2020;25:e160–9.
pubmed: 31395751
doi: 10.1634/theoncologist.2019-0297
Smyth LM, et al. Capivasertib, an AKT kinase inhibitor, as monotherapy or in combination with fulvestrant in patients with AKT1 E17K-mutant, ER-positive metastatic breast cancer. Clin Cancer Res. 2020;26:3947–57.
pubmed: 32312891
pmcid: 7415507
doi: 10.1158/1078-0432.CCR-19-3953
Banerji U, et al. A phase I open-label study to identify a dosing regimen of the pan-AKT inhibitor AZD5363 for evaluation in solid tumors and in PIK3CA-mutated breast and gynecologic cancers. Clin Cancer Res. 2018;24:2050–9.
pubmed: 29066505
doi: 10.1158/1078-0432.CCR-17-2260
Turner NC, et al. BEECH: a dose-finding run-in followed by a randomised phase II study assessing the efficacy of AKT inhibitor capivasertib (AZD5363) combined with paclitaxel in patients with estrogen receptor-positive advanced or metastatic breast cancer, and in a PIK3CA mutant sub-population. Ann Oncol. 2019;30:774–80.
pubmed: 30860570
pmcid: 6551452
doi: 10.1093/annonc/mdz086
Oliveira M, et al. FAIRLANE, a double-blind placebo-controlled randomized phase II trial of neoadjuvant ipatasertib plus paclitaxel for early triple-negative breast cancer. Ann Oncol. 2019;30:1289–97.
pubmed: 31147675
doi: 10.1093/annonc/mdz177
Mayer IA, et al. A phase Ib study of alpelisib (BYL719), a PI3Kα-specific inhibitor, with letrozole in ER+/HER2-negative metastatic breast cancer. Clin Cancer Res. 2017;23:26.
pubmed: 27126994
doi: 10.1158/1078-0432.CCR-16-0134
Pistilli B, et al. Phase II study of buparlisib (BKM120) and trastuzumab in patients with HER2+ locally advanced or metastatic breast cancer resistant to trastuzumab-based therapy. Breast Cancer Res Treat. 2018;168:357.
pubmed: 29198055
doi: 10.1007/s10549-017-4596-7
Bendell JC, et al. Phase I, dose-escalation study of BKM120, an oral pan-class I PI3K inhibitor, in patients with advanced solid tumors. J Clin Oncol. 2012;30:282–90.
pubmed: 22162589
doi: 10.1200/JCO.2011.36.1360
Mayer IA, et al. Stand up to cancer phase Ib study of pan-phosphoinositide-3-kinase inhibitor buparlisib with letrozole in estrogen receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2014;32:1202–9.
pubmed: 24663045
pmcid: 3986383
doi: 10.1200/JCO.2013.54.0518
Rodon J, et al. A Phase Ib, open-label, dose-finding study of alpelisib in combination with paclitaxel in patients with advanced solid tumors. Oncotarget. 2018;9:31709–18.
pubmed: 30167089
pmcid: 6114962
doi: 10.18632/oncotarget.25854
Saura C, et al. Neoadjuvant letrozole plus taselisib versus letrozole plus placebo in postmenopausal women with oestrogen receptor-positive, HER2-negative, early-stage breast cancer (LORELEI): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2019;20:1226–38.
pubmed: 31402321
doi: 10.1016/S1470-2045(19)30334-1
Ma CX, et al. A phase i trial of the IGF-1R antibody Cixutumumab in combination with temsirolimus in patients with metastatic breast cancer. Breast Cancer Res Treat. 2013;139:145–53.
pubmed: 23605083
pmcid: 4517667
doi: 10.1007/s10549-013-2528-8
Malorni L, et al. Serum thymidine kinase activity in patients with hormone receptor-positive and HER2-negative metastatic breast cancer treated with palbociclib and fulvestrant. Eur J Cancer. 2022;164:39–51.
pubmed: 35172272
doi: 10.1016/j.ejca.2021.12.030
Mayer IA, et al. A Phase II randomized study of neoadjuvant letrozole plus alpelisib for hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer (NEO-ORB). Clin Cancer Res. 2019;25:2975–87.
pubmed: 30723140
pmcid: 6522303
doi: 10.1158/1078-0432.CCR-18-3160
Juric D, et al. Alpelisib plus fulvestrant in PIK3CA-altered and PIK3CA-wild-type estrogen receptor-positive advanced breast cancer: a phase 1b clinical trial. JAMA Oncol. 2019;5:e184475–e184475.
pubmed: 30543347
doi: 10.1001/jamaoncol.2018.4475
Juric D, et al. Phosphatidylinositol 3-Kinase α-selective inhibition with alpelisib (BYL719) in PIK3CA-altered solid tumors: results from the first-in-human study. J Clin Oncol. 2018;36:1291–9.
pubmed: 29401002
pmcid: 5920739
doi: 10.1200/JCO.2017.72.7107
Sharma P, et al. Clinical and biomarker results from phase I/II study of PI3K inhibitor alpelisib plus nab-paclitaxel in HER2-negative metastatic breast cancer. Clin Cancer Res. 2021;27:3896–904.
pubmed: 33602685
pmcid: 8282704
doi: 10.1158/1078-0432.CCR-20-4879
Rugo HS, et al. Alpelisib plus fulvestrant in PIK3CA-mutated, hormone receptor-positive advanced breast cancer after a CDK4/6 inhibitor (BYLieve): one cohort of a phase 2, multicentre, open-label, non-comparative study. Lancet Oncol. 2021;22:489–98.
pubmed: 33794206
doi: 10.1016/S1470-2045(21)00034-6
Ma CX, et al. A phase 1 trial of BKM120 (Buparlisib) in combination with fulvestrant in postmenopausal women with estrogen receptor positive metastatic breast cancer. Clin Cancer Res. 2016;22:1583.
pubmed: 26563128
doi: 10.1158/1078-0432.CCR-15-1745
Schmid P, et al. Capivasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer: the PAKT trial. J Clin Oncol. 2020;38:423–33.
pubmed: 31841354
doi: 10.1200/JCO.19.00368
Howell SJ, et al. Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor-positive, HER2-negative breast cancer (FAKTION): overall survival, updated progression-free survival, and expanded biomarker analysis from a randomised, phase 2 trial. Lancet Oncol. 2022;23:851–64.
pubmed: 35671774
pmcid: 9630162
doi: 10.1016/S1470-2045(22)00284-4
Jones RH, et al. Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor-positive breast cancer (FAKTION): a multicentre, randomised, controlled, phase 2 trial. Lancet Oncol. 2020;21:345–57.
pubmed: 32035020
pmcid: 7052734
doi: 10.1016/S1470-2045(19)30817-4
Gombos A, et al. FDG positron emission tomography imaging and ctDNA detection as an early dynamic biomarker of everolimus efficacy in advanced luminal breast cancer. NPJ Breast Cancer. 2021;7:1–9.
doi: 10.1038/s41523-021-00331-8
Kornblum N, et al. Randomized phase II trial of fulvestrant plus everolimus or placebo in postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer resistant to aromatase inhibitor therapy: results of PrE0102. J Clin Oncol. 2018;36:1556–63.
pubmed: 29664714
pmcid: 7186582
doi: 10.1200/JCO.2017.76.9331
Van Swearingen AED, et al. LCCC 1025: a phase II study of everolimus, trastuzumab, and vinorelbine to treat progressive HER2-positive breast cancer brain metastases. Breast Cancer Res Treat. 2018;171:637–48.
pubmed: 29938395
pmcid: 6779035
doi: 10.1007/s10549-018-4852-5
Singh JC, et al. Phase 2 trial of everolimus and carboplatin combination in patients with triple negative metastatic breast cancer. Breast Cancer Res. 2014;16:R32.
pubmed: 24684785
pmcid: 4053575
doi: 10.1186/bcr3634
Rugo HS, et al. Prevention of everolimus-related stomatitis in women with hormone receptor-positive, HER2-negative metastatic breast cancer using dexamethasone mouthwash (SWISH): a single-arm, phase 2 trial. Lancet Oncol. 2017;18:654–62.
pubmed: 28314691
doi: 10.1016/S1470-2045(17)30109-2
Ballhausen A, et al. Phase I study of everolimus, letrozole, and trastuzumab in patients with hormone receptor-positive metastatic breast cancer or other solid tumors. Clin Cancer Res. 2021;27:1247–55.
pubmed: 33115815
doi: 10.1158/1078-0432.CCR-20-2878
Peddi PF, et al. Phase II randomized trial of a non-steroidal mouth wash for prevention and treatment of stomatitis in women with hormone receptor positive breast cancer treated with everolimus. Ther Adv Med Oncol. 2020;12:1758835920967259.
pubmed: 33299473
pmcid: 7711222
doi: 10.1177/1758835920967259
Jones VE, et al. Evaluation of miracle mouthwash plus hydrocortisone versus prednisolone mouth rinses as prophylaxis for everolimus-associated stomatitis: a randomized phase II study. Oncologist. 2019;24:1153–8.
pubmed: 30833486
pmcid: 6738305
doi: 10.1634/theoncologist.2018-0340
Maass N, et al. Everolimus as treatment for breast cancer patients with bone metastases only: results of the phase II RADAR study. J Cancer Res Clin Oncol. 2013;139:2047–56.
pubmed: 24072232
doi: 10.1007/s00432-013-1518-x
Alsaleh K, et al. Neoadjuvant endocrine therapy with or without palbociclib in low-risk patients: a phase III randomized double-blind SAFIA trial. J Cancer Res Clin Oncol. 2023. https://doi.org/10.1007/S00432-023-04588-3 .
doi: 10.1007/S00432-023-04588-3
pubmed: 36680581
pmcid: 9864499
Loibl S, et al. Palbociclib for residual high-risk invasive HR-positive and HER2-negative early breast cancer-the penelope-B trial. J Clin Oncol. 2021;39:1518–30.
pubmed: 33793299
doi: 10.1200/JCO.20.03639
Krop IE, et al. Trastuzumab emtansine plus pertuzumab versus taxane plus trastuzumab plus pertuzumab after anthracycline for high-risk human epidermal growth factor receptor 2-positive early breast cancer: the phase III KAITLIN study. J Clin Oncol. 2022;40:438–48.
pubmed: 34890214
doi: 10.1200/JCO.21.00896
André F, et al. Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2014;15:580–91.
pubmed: 24742739
doi: 10.1016/S1470-2045(14)70138-X
Baselga J, et al. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012;379:633–40.
pubmed: 22257673
pmcid: 5705192
doi: 10.1016/S0140-6736(11)61847-3
Untch M, et al. Lapatinib versus trastuzumab in combination with neoadjuvant anthracycline-taxane-based chemotherapy (GeparQuinto, GBG 44): a randomised phase 3 trial. Lancet Oncol. 2012;13:135–44.
pubmed: 22257523
doi: 10.1016/S1470-2045(11)70397-7
Moore HCF, et al. A randomized trial of fulvestrant, everolimus, and anastrozole for the front-line treatment of patients with advanced hormone receptor-positive breast cancer, SWOG S1222. Clin Cancer Res. 2022;28:611–7.
pubmed: 34844978
pmcid: 9782801
doi: 10.1158/1078-0432.CCR-21-3131
Guarneri V, et al. Everolimus plus aromatase inhibitors as maintenance therapy after first-line chemotherapy: final results of the phase III randomised MAIN-A (MAINtenance Afinitor) trial. Eur J Cancer. 2021;154:21–9.
pubmed: 34225066
doi: 10.1016/j.ejca.2021.05.008
Im YH, et al. Safety and efficacy of everolimus (EVE) plus exemestane (EXE) in postmenopausal women with locally advanced or metastatic breast cancer: final results from EVEREXES. Breast Cancer Res Treat. 2021;188:77–89.
pubmed: 33728524
doi: 10.1007/s10549-021-06173-z
Jerusalem G, et al. Safety of everolimus plus exemestane in patients with hormone-receptor-positive, HER2-negative locally advanced or metastatic breast cancer progressing on prior non-steroidal aromatase inhibitors: primary results of a phase IIIb, open-label, single-arm, expanded-access multicenter trial (BALLET). Ann Oncol. 2016;27:1719–25.
pubmed: 27358383
doi: 10.1093/annonc/mdw249
Lehmann BD, et al. Atezolizumab in combination with carboplatin and survival outcomes in patients with metastatic triple-negative breast cancer: the TBCRC 043 phase 2 randomized clinical trial. JAMA Oncol. 2024;10:193–201.
pubmed: 38095878
doi: 10.1001/jamaoncol.2023.5424
DeCensi A, et al. Lapatinib activity in premalignant lesions and HER-2-positive cancer of the breast in a randomized, placebo-controlled presurgical trial. Cancer Prev Res. 2011;4:1181–9.
doi: 10.1158/1940-6207.CAPR-10-0337
Franzoi MA, Lambertini M, Ceppi M, Bruzzone M, de Azambuja E. Implication of body mass index (BMI) on the biological and clinical effects of endocrine therapy plus abemaciclib as neoadjuvant therapy for early breast cancer patients. Breast Cancer Res Treat. 2022;192:457–62.
pubmed: 35076812
doi: 10.1007/s10549-022-06525-3
Martel S, et al. Body mass index and weight change in patients With HER2-positive early breast cancer: exploratory analysis of the ALTTO BIG 2–06 trial. J Natl Compr Canc Netw. 2021;19:181–9.
pubmed: 33401235
doi: 10.6004/jnccn.2020.7606
Di Cosimo S, et al. Effect of body mass index on response to neo-adjuvant therapy in HER2-positive breast cancer: an exploratory analysis of the NeoALTTO trial. Breast Cancer Res. 2020;22:1–7.
doi: 10.1186/s13058-020-01356-w
Pfeiler G, et al. Impact of body mass index on treatment and outcomes in patients with early hormone receptor-positive breast cancer receiving endocrine therapy with or without palbociclib in the PALLAS trial. J Clin Oncol. 2022;40(16_suppl):518–518.
doi: 10.1200/JCO.2022.40.16_suppl.518
Franzoi MA, et al. Clinical implications of body mass index in metastatic breast cancer patients treated with abemaciclib and endocrine therapy. J Nat Cancer Inst. 2021;113:462–70.
pubmed: 32750143
doi: 10.1093/jnci/djaa116
Weight-Based Dosing vs Fixed Dosing of Pembrolizumab: an Economic Analysis – Hematology & Oncology. https://www.hematologyandoncology.net/archives/august-2018/weight-based-dosing-vs-fixed-dosing-of-pembrolizumab-an-economic-analysis/ .
Hall E, et al. Economics of alternative dosing strategies for pembrolizumab and nivolumab at a single academic cancer center. Cancer Med. 2020;9:2106–12.
pubmed: 31994335
pmcid: 7064089
doi: 10.1002/cam4.2888
Freshwater T, et al. Evaluation of dosing strategy for pembrolizumab for oncology indications. J Immunother Cancer. 2017;5:1–9.
doi: 10.1186/s40425-017-0242-5
Ji Y, Jin JY, Hyman DM, Kim G, Suri A. Challenges and opportunities in dose finding in oncology and immuno-oncology. Clin Transl Sci. 2018;11:345–51.
pubmed: 29392871
pmcid: 6039198
doi: 10.1111/cts.12540
Murphy R, Halford S, Symeonides SN. Project optimus, an FDA initiative: considerations for cancer drug development internationally, from an academic perspective. Front Oncol. 2023;13:1144056.
pubmed: 36937434
pmcid: 10020863
doi: 10.3389/fonc.2023.1144056
Griggs JJ, et al. Appropriate systemic therapy dosing for obese adult patients with cancer: ASCO Guideline update. J Clin Oncol. 2021;39:2037–48.
pubmed: 33939491
doi: 10.1200/JCO.21.00471
Silvestris N, et al. Antineoplastic dosing in overweight and obese cancer patients: an Associazione Italiana Oncologia Medica (AIOM)/Associazione Medici Diabetologi (AMD)/Società Italiana Endocrinologia (SIE)/Società Italiana Farmacologia (SIF) multidisciplinary consensus position paper. ESMO Open. 2021;6:100153.
pubmed: 33984679
pmcid: 8134762
doi: 10.1016/j.esmoop.2021.100153
Daousi C, et al. Prevalence of obesity in type 2 diabetes in secondary care: association with cardiovascular risk factors. Postgrad Med J. 2006;82:280.
pubmed: 16597817
pmcid: 2579635
doi: 10.1136/pmj.2005.039032
Mandal A. Study of prevalence of type 2 diabetes mellitus and hypertension in overweight and obese people. J Family Med Prim Care. 2014;3:25.
pubmed: 24791232
pmcid: 4005195
doi: 10.4103/2249-4863.130265
Regmi D, Al-Shamsi S, Govender RD, Al Kaabi J. Incidence and risk factors of type 2 diabetes mellitus in an overweight and obese population: a long-term retrospective cohort study from a Gulf state. BMJ Open. 2020;10:e035813.
pubmed: 32616491
pmcid: 7333876
doi: 10.1136/bmjopen-2019-035813
Wang Y, Beydoun MA. The obesity epidemic in the United States–gender, age, socioeconomic, racial/ethnic, and geographic characteristics: a systematic review and meta-regression analysis. Epidemiol Rev. 2007;29:6–28.
pubmed: 17510091
doi: 10.1093/epirev/mxm007
Anekwe CV, et al. Socioeconomics of obesity. Curr Obes Rep. 2020;9:272.
pubmed: 32627133
pmcid: 7484407
doi: 10.1007/s13679-020-00398-7
Bandera EV, Maskarinec G, Romieu I, John EM. Racial and ethnic disparities in the impact of obesity on breast cancer risk and survival: a global perspective. Adv Nutr. 2015;6:803.
pubmed: 26567202
pmcid: 4642425
doi: 10.3945/an.115.009647
Pasco JA, Nicholson GC, Brennan SL, Kotowicz MA. Prevalence of obesity and the relationship between the body mass index and body fat: cross-sectional, population-based data. PLoS ONE. 2012;7:e29580.
pubmed: 22253741
pmcid: 3258232
doi: 10.1371/journal.pone.0029580
Ho-Pham LT, Lai TQ, Nguyen MTT, Nguyen TV. Relationship between body mass index and percent body fat in vietnamese: implications for the diagnosis of obesity. PLoS One. 2015;10:e0127198.
pubmed: 26018910
pmcid: 4446298
doi: 10.1371/journal.pone.0127198
Shachar SS, Williams GR. The obesity paradox in cancer-moving beyond BMI. Cancer Epidemiol Biomarkers Prev. 2017;26:13–6.
pmcid: 5830139
doi: 10.1158/1055-9965.EPI-16-0439
Tafeit E, et al. Using body mass index ignores the intensive training of elite special force personnel. Exp Biol Med. 2019;244:873.
doi: 10.1177/1535370219848986
Banack HR, Wactawski-Wende J, Hovey KM, Stokes A. Is BMI a valid measure of obesity in post-menopausal women? Menopause. 2018;25:307.
pubmed: 29135897
pmcid: 5821529
doi: 10.1097/GME.0000000000000989
Silvestris N, et al. Antineoplastic dosing in overweight and obese cancer patients: an Associazione Italiana Oncologia Medica (AIOM)/Associazione Medici Diabetologi (AMD)/Società Italiana Endocrinologia (SIE)/Società Italiana Farmacologia (SIF) multidisciplinary consensus position paper. ESMO Open. 2021;6:100153.
pubmed: 33984679
pmcid: 8134762
doi: 10.1016/j.esmoop.2021.100153
Isnaldi E, et al. Digital analysis of distant and cancer-associated mammary adipocytes. Breast Off J Eur Soc Mastol. 2020;54:179.
Umscheid CA, Margolis DJ, Grossman CE. Key concepts of clinical trials: a narrative review. Postgrad Med. 2011;123:194.
pubmed: 21904102
pmcid: 3272827
doi: 10.3810/pgm.2011.09.2475
Malik L, Lu D. Eligibility criteria for phase I clinical trials: tight vs loose? Cancer Chemother Pharmacol. 2019;83:999–1002.
pubmed: 30809701
doi: 10.1007/s00280-019-03801-w
He J, Morales DR, Guthrie B. Exclusion rates in randomized controlled trials of treatments for physical conditions: a systematic review. Trials. 2020;21:1–11.
doi: 10.1186/s13063-020-4139-0
Lynce F, et al. Abstract CT142: TALAVE: Induction talazoparib (tala) followed by combined tala and avelumab in patients (pts) with advanced breast cancer (ABC). Cancer Res. 2023;83:CT142.
doi: 10.1158/1538-7445.AM2023-CT142
Hong R, et al. Palbociclib, trastuzumab, pyrotinib and fulvestrant in patients with brain metastasis from ER/PR positive, HER-2 positive breast cancer: Report from an interim analysis of a multicenter, prospective study in China, 2023;41: e13032–e13032. https://doi.org/10.1200/JCO.2023.41.16_suppl.e13032
Van Den Bogert CA, et al. Non-publication is common among phase 1, single-center, not prospectively registered, or early terminated clinical drug trials. PLoS ONE. 2016;11:e0167709.
pubmed: 27973571
pmcid: 5156378
doi: 10.1371/journal.pone.0167709