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Patient-centered dosing: oncologists’ perspectives about treatment-related side effects and individualized dosing for patients with metastatic breast cancer (MBC)

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Abstract

Purpose

Although metastatic breast cancer (MBC) is treatable, it is not curable and most patients remain on treatment indefinitely. While oncologists commonly prescribe the recommended starting dose (RSD) from the FDA-approved label, patient tolerance may differ from that seen in clinical trials. We report on a survey of medical oncologists’ perspectives about treatment-related toxicity and willingness to discuss flexible dosing with patients.

Methods

We disseminated a confidential survey via social media/email in Spring 2021. Eligible respondents needed to be US-based medical oncologists with experience treating patients with MBC.

Results

Of 131 responses, 119 were eligible. Physicians estimated that 47% of their patients reported distressing treatment-related side effects; of these, 15% visited the Emergency Room/hospital and 37% missed treatment. 74% (n = 87) of doctors reported improvement of patient symptoms after dose reduction. 87% (n = 104) indicated that they had ever, if appropriate, initiated treatment at lower doses. Most (85%, n = 101) respondents did not believe that the RSD is always more effective than a lower dose and 97% (n = 115) were willing to discuss individualized dosing with patients.

Conclusion

Treatment-related side effects are prevalent among patients with MBC, resulting in missed treatments and acute care visits. To help patients tolerate treatment, oncologists may decrease initial and/or subsequent doses. The majority of oncologists reject the premise that a higher dose is always superior and are willing to discuss individualized dosing with patients. Given potential improvements regarding quality of life and clinical care, dose modifications should be part of routine shared decision-making between patients and oncologists.

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Data availability

The dataset used in this study may be available from the corresponding author upon reasonable request.

References

  1. Jones SE (2008) Metastatic breast cancer: the treatment challenge. Clin Breast Cancer 8:224–233

    Article  CAS  PubMed  Google Scholar 

  2. Minasian L, Rosen O, Auclair D, Rahman A, Pazdur R, Schilsky R (2014) Optimizing dosing of oncology drugs. Clin Pharmacol Ther 96:572–579

    Article  CAS  PubMed  Google Scholar 

  3. Ratain MJ, Tannock IF, Lichter AS (2021) Dose optimization of sotorasib: is the US Food and Drug Administration sending a message? J Clin Oncol 39:3423–3426

    Article  PubMed  Google Scholar 

  4. Kuchuk I, Bouganim N, Beusterien K, Grinspan J, Vandermeer L, Gertler S, Dent S, Song X, Segal R, Mazzarello S (2013) Preference weights for chemotherapy side effects from the perspective of women with breast cancer. Breast Cancer Res Treat 142:101–107

    Article  CAS  PubMed  Google Scholar 

  5. Wood R, Mitra D, de Courcy J, Iyer S (2017) Patient-reported quality of life and treatment satisfaction in patients with HR+/HER2–advanced/metastatic breast cancer. Clin Ther 39:1719–1728

    Article  PubMed  Google Scholar 

  6. Cardoso F, Di Leo A, Lohrisch C, Bernard C, Ferreira F, Piccart M (2002) Second and subsequent lines of chemotherapy for metastatic breast cancer: what did we learn in the last two decades? Ann Oncol 13:197–207

    Article  CAS  PubMed  Google Scholar 

  7. Shah M, Rahman A, Theoret MR, Pazdur R (2021) The drug-dosing conundrum in oncology-when less is more. N Engl J Med 385:1445–1447

    Article  PubMed  Google Scholar 

  8. Cleeland CS, Allen JD, Roberts SA, Brell JM, Giralt SA, Khakoo AY, Kirch RA, Kwitkowski VE, Liao Z, Skillings J (2012) Reducing the toxicity of cancer therapy: recognizing needs, taking action. Nat Rev Clin Oncol 9:471–478

    Article  CAS  PubMed  Google Scholar 

  9. Carlson M (2021) When the ‘Maximum Tolerable Dose’ of Cancer Treatment Isn’t Tolerable. Cure Today. https://www.curetoday.com/view/when-the-maximum-tolerable-dose-of-cancer-treatment-isn-t-tolerable. Accessed 22 March 2022

  10. Nanda S (2021) Patient survey points to need for innovative dosing strategies in MBC. Medicine Matters. https://oncology.medicinematters.com/asco-2021/breast-cancer/patient-advocate-led-survey-innovative-drugdosing/19251100. Accessed 22 March 2022

  11. Ratain MJ (2014) Redefining the primary objective of phase I oncology trials. Nat Rev Clin Oncol 11:503–504

    Article  CAS  PubMed  Google Scholar 

  12. Nie L, Rubin EH, Mehrotra N, Pinheiro J, Fernandes LL, Roy A, Bailey S, de Alwis DP (2016) Rendering the 3+ 3 design to rest: more efficient approaches to oncology dose-finding trials in the era of targeted therapy. Clin Cancer Res 22:2623–2629

    Article  CAS  PubMed  Google Scholar 

  13. Norris DC (2017) Dose titration algorithm tuning (DTAT) should supersede ‘the’ maximum tolerated dose (MTD) in oncology dose-finding trials. F1000Research 6:112

    Article  PubMed  PubMed Central  Google Scholar 

  14. Subbiah V, Kurzrock R (2018) Challenging standard-of-care paradigms in the precision oncology era. Trends Cancer 4:101–109

    Article  PubMed  PubMed Central  Google Scholar 

  15. Mandrekar SJ, Cui Y, Sargent DJ (2007) An adaptive phase I design for identifying a biologically optimal dose for dual agent drug combinations. Stat Med 26:2317–2330

    Article  PubMed  Google Scholar 

  16. Ratain MJ, Strohbehn GW, Tannock IF, Lichter (2021) Optimize the dose: An optimal step forward for FDA. Periodical: The Cancer Letter. 47(23): https://cancerletter.com/guest-editorial/20210611_4/. Accessed 22 March 2022

  17. Jänne PA, Kim G, Shaw AT, Sridhara R, Pazdur R, McKee AE (2016) Dose finding of small-molecule oncology drugs: optimization throughout the development life cycle. Clin Cancer Res 22:2613–2617. https://doi.org/10.1158/1078-0432.Ccr-15-2643

    Article  PubMed  Google Scholar 

  18. Le Tourneau C, Lee JJ, Siu LL (2009) Dose escalation methods in phase I cancer clinical trials. JNCI J Natl Cancer Inst 101:708–720

    Article  PubMed  Google Scholar 

  19. Gennari A, Sun Z, Hasler-Strub U, Colleoni M, Kennedy MJ, Von Moos R, Cortés J, Vidal MJ, Hennessy B, Walshe J, Parraga KA, Ribi K, Bernhard J, Murillo SM, Pagani O, Barbeaux A, Borstnar S, Rabaglio-Poretti M, Maibach R, Regan MM, Jerusalem G (2018) A randomized phase II study evaluating different maintenance schedules of nab-paclitaxel in the first-line treatment of metastatic breast cancer: final results of the IBCSG 42–12/BIG 2–12 SNAP trial. Ann Oncol 29:661–668. https://doi.org/10.1093/annonc/mdx772

    Article  CAS  PubMed  Google Scholar 

  20. Leonard R, Hennessy BT, Blum JL, O’Shaughnessy J (2011) Dose-adjusting capecitabine minimizes adverse effects while maintaining efficacy: a retrospective review of capecitabine for metastatic breast cancer. Clin Breast Cancer 11:349–356

    Article  CAS  PubMed  Google Scholar 

  21. Stadtmauer EA, O’Neill A, Goldstein LJ, Crilley PA, Mangan KF, Ingle JN, Brodsky I, Martino S, Lazarus HM, Erban JK (2000) Conventional-dose chemotherapy compared with high-dose chemotherapy plus autologous hematopoietic stem-cell transplantation for metastatic breast cancer. N Engl J Med 342:1069–1076

    Article  CAS  PubMed  Google Scholar 

  22. Goutsouliak K, Veeraraghavan J, Sethunath V, De Angelis C, Osborne CK, Rimawi MF, Schiff R (2020) Towards personalized treatment for early stage HER2-positive breast cancer. Nat Rev Clin Oncol 17:233–250. https://doi.org/10.1038/s41571-019-0299-9

    Article  PubMed  Google Scholar 

  23. Sheen MA, Apuri S, Ismail-Khan R (2016) Progression free survival and toxicity with dose variations of everolimus in metastatic hormone receptor positive breast cancer. J Clin Oncol 34:e12058–e12058. https://doi.org/10.1200/JCO.2016.34.15_suppl.e12058

    Article  Google Scholar 

  24. Project Optimus. FDA

  25. Sachs JR, Mayawala K, Gadamsetty S, Kang SP, de Alwis DP (2016) Optimal dosing for targeted therapies in oncology: drug development cases leading by example. Clin Cancer Res 22:1318–1324

    Article  CAS  PubMed  Google Scholar 

  26. Peck RW (2018) Precision medicine is not just genomics: the right dose for every patient. Annu Rev Pharmacol Toxicol 58:105–122

    Article  CAS  PubMed  Google Scholar 

  27. Blumenthal G, Jain L, Loeser AL, Pithaval YK, Rahman A, Ratain MJ, Shah M, Strawn L, Theoret MR (2021) Optimizing dosing in oncology drug development. Friends Cancer Res pp 1–14

  28. Dreyer MS, Kacew A, Hsieh P-H, Serritella A, Knoebel RW, Nanda R, Strohbehn GW, Ratain MJ (2021) Patient out-of-pocket savings with lower-dose trastuzumab. J Clin Oncol 39:e18828–e18828. https://doi.org/10.1200/JCO.2021.39.15_suppl.e18828

    Article  Google Scholar 

  29. (2021) Amgen Provides Updated Information On LUMAKRAS™ (Sotorasib)1 Dose comparison study. In: PR Newswire, Thousand Oaks, CA

  30. (2020) About Us. In: Patient Centered Dosing Initiative

  31. Loeser AL, Peppercorn JM, Burkard ME, Kalinsky K, Rugo HS, Bardia A (2021) Treatment-related side effects and views about dosage assessment to sustain quality of life: results of an advocate-led survey of patients with metastatic breast cancer (MBC). J Clin Oncol 39:1005

    Article  Google Scholar 

  32. Loeser AL, Bardia A, Burkard ME, Kalinsky KM, Peppercorn J, Rugo HS, Carlson M, Cowden J, Maues J, McGlown S (2022) Abstract P4-10-09: patient-centered dosing: oncologists’ perspectives about treatment-related side effects and individualized dosing for patients with metastatic breast cancer (MBC). Cancer Res 82:P4-10-09-P14-10-09

    Article  Google Scholar 

  33. R Core Team (2020) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria

    Google Scholar 

  34. Fromme EK, Eilers KM, Mori M, Hsieh Y-C, Beer TM (2004) How accurate is clinician reporting of chemotherapy adverse effects? A comparison with patient-reported symptoms from the Quality-of-Life Questionnaire C30. J Clin Oncol 22:3485–3490

    Article  PubMed  Google Scholar 

  35. Behroozian T, Milton L, Zhang L, Lou J, Karam I, Lam E, Wong G, Szumacher E, Chow E (2021) How do patient-reported outcomes compare with clinician assessments? A prospective study of radiation dermatitis in breast cancer. Radiother Oncol 159:98–105

    Article  PubMed  Google Scholar 

  36. Di Maio M, Gallo C, Leighl NB, Piccirillo MC, Daniele G, Nuzzo F, Gridelli C, Gebbia V, Ciardiello F, De Placido S (2015) Symptomatic toxicities experienced during anticancer treatment: agreement between patient and physician reporting in three randomized trials. J Clin Oncol 33(8):910–915

    Article  PubMed  Google Scholar 

  37. Gravis G, Marino P, Joly F, Oudard S, Priou F, Esterni B, Latorzeff I, Delva R, Krakowski I, Laguerre B (2014) Patients’ self-assessment versus investigators’ evaluation in a phase III trial in non-castrate metastatic prostate cancer (GETUG-AFU 15). Eur J Cancer 50:953–962

    Article  PubMed  Google Scholar 

  38. Atkinson TM, Ryan SJ, Bennett AV, Stover AM, Saracino RM, Rogak LJ, Jewell ST, Matsoukas K, Li Y, Basch E (2016) The association between clinician-based common terminology criteria for adverse events (CTCAE) and patient-reported outcomes (PRO): a systematic review. Support Care Cancer 24:3669–3676

    Article  PubMed  PubMed Central  Google Scholar 

  39. Veitch ZW, Shepshelovich D, Gallagher C, Wang L, Abdul Razak AR, Spreafico A, Bedard PL, Siu LL, Minasian L, Hansen AR (2021) Underreporting of symptomatic adverse events in phase I clinical trials. JNCI J Natl Cancer Inst 113:980–988

    Article  PubMed  Google Scholar 

  40. Basch E, Jia X, Heller G, Barz A, Sit L, Fruscione M, Appawu M, Iasonos A, Atkinson T, Goldfarb S (2009) Adverse symptom event reporting by patients vs clinicians: relationships with clinical outcomes. JNCI J Natl Cancer Inst 101:1624–1632

    Article  PubMed  Google Scholar 

  41. Mayer M (2014) Living with advanced breast cancer: challenges and opportunities. Breast 20:S12–S13. https://doi.org/10.1016/j.breast.2011.08.004

    Article  Google Scholar 

  42. Tanay M, Armes J, Ream E (2017) The experience of chemotherapy-induced peripheral neuropathy in adult cancer patients: a qualitative thematic synthesis. Eur J Cancer Care 26:e12443

    Article  Google Scholar 

  43. Breetvelt I, Van Dam F (1991) Underreporting by cancer patients: the case of response-shift. Soc Sci Med 32:981–987

    Article  CAS  PubMed  Google Scholar 

  44. (2014) Metastatic breast cancer landscape analysis: research report. MBC Alliance, New York, NY

  45. Markman M (2006) Chemotherapy-induced peripheral neuropathy: underreported and underappreciated. Curr Pain Headache Rep 10:275–278

    Article  PubMed  Google Scholar 

  46. Rao A, Cohen HJ (2004) Symptom management in the elderly cancer patient: fatigue, pain, and depression. JNCI Monogr 2004:150–157

    Article  Google Scholar 

  47. Rogatko A, Babb JS, Tighiouart M, Khuri FR, Hudes G (2005) New paradigm in dose-finding trials: patient-specific dosing and beyond phase I. Clin Cancer Res 11:5342–5346

    Article  CAS  PubMed  Google Scholar 

  48. Mathijssen RH, Sparreboom A, Verweij J (2014) Determining the optimal dose in the development of anticancer agents. Nat Rev Clin Oncol 11:272–281

    Article  CAS  PubMed  Google Scholar 

  49. Piccart MJ, Hilbers FS, Bliss JM, Caballero C, Frank ES, Renault P, Naït Kaoudjt R, Schumacher E, Spears PA, Regan MM, Gelber RD, Davidson NE, Norton L, Winer EP (2020) Road map to safe and well-designed de-escalation trials of systemic adjuvant therapy for solid tumors. J Clin Oncol 38:4120–4129. https://doi.org/10.1200/jco.20.01382

    Article  CAS  PubMed  Google Scholar 

  50. Hart LL, Bardia A, Beck JT, Chan A, Neven P, Hamilton EP, Sohn J, Sonke GS, Bachelot T, Spring L, Gac FL, Hu H, Gao M, Laurentiis MD (2022) Impact of ribociclib (RIB) dose modifications (mod) on overall survival (OS) in patients (pts) with HR+/HER2- advanced breast cancer (ABC) in MONALEESA(ML)-2. J Clin Oncol 40:1017–1017. https://doi.org/10.1200/JCO.2022.40.16_suppl.1017

    Article  Google Scholar 

  51. Xie X, Wu Y, Luo S, Yang H, Li L, Zhou S, Shen R, Lin H (2017) Efficacy and toxicity of low-dose versus conventional-dose chemotherapy for malignant tumors: a meta-analysis of 6 randomized controlled trials. Asian Pac J Cancer Prev 18:479–484. https://doi.org/10.22034/apjcp.2017.18.2.479

    Article  PubMed  PubMed Central  Google Scholar 

  52. Jain RK, Lee JJ, Hong D, Markman M, Gong J, Naing A, Wheler J, Kurzrock R (2010) Phase I oncology studies: evidence that in the era of targeted therapies patients on lower doses do not fare worse. Clin Cancer Res 16:1289–1297. https://doi.org/10.1158/1078-0432.Ccr-09-2684

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Barcenas C, Hurvitz S, Di Palma J, Bose R, Chien A, Iannotti N, Marx G, Brufsky A, Litvak A, Ibrahim E (2020) Improved tolerability of neratinib in patients with HER2-positive early-stage breast cancer: the CONTROL trial. Ann Oncol 31:1223–1230

    Article  CAS  PubMed  Google Scholar 

  54. Pelosci A (2021) FDA approves dose-escalation label amendment for neratinib in HER2+ breast cancer. CancerNetwork https://www.cancernetwork.com/view/fda-approves-dose-escalation-label-amendment-forneratinib-in-her2-breast-cancer. Accessed 4 April 2022

  55. Martins Y, Lederman R, Lowenstein C, Joffe S, Neville B, Hastings B, Abel G (2012) Increasing response rates from physicians in oncology research: a structured literature review and data from a recent physician survey. Br J Cancer 106:1021–1026

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Gradishar WJ, Tjulandin S, Davidson N, Shaw H, Desai N, Bhar P, Hawkins M, O’Shaughnessy J (2005) Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil–based paclitaxel in women with breast cancer. J Clin Oncol 23:7794–7803

    Article  CAS  PubMed  Google Scholar 

  57. Blum JL, Jones SE, Buzdar AU, LoRusso PM, Kuter I, Vogel C, Osterwalder B, Burger H-U, Brown CS, Griffin T (1999) Multicenter phase II study of capecitabine in paclitaxel-refractory metastatic breast cancer. J Clin Oncol 17:485–485

    Article  CAS  PubMed  Google Scholar 

  58. Hennessy B, Gauthier A, Michaud L, Hortobagyi G, Valero V (2005) Lower dose capecitabine has a more favorable therapeutic index in metastatic breast cancer: retrospective analysis of patients treated at MD Anderson Cancer Center and a review of capecitabine toxicity in the literature. Ann Oncol 16:1289–1296

    Article  CAS  PubMed  Google Scholar 

  59. Suresh A, Ganju A, Morgan E, Palettas M, Stephens JA, Liu J, Berger M, Vargo C, Noonan A, Reinbolt R, Cherian M, VanDeusen J, Sardesai S, Wesolowski R, Stover DG, Lustberg M, Ramaswamy B, Williams N (2020) Efficacy of different dosing schedules of capecitabine for metastatic breast cancer: a single-institution experience. Investig New Drugs 38:1605–1611. https://doi.org/10.1007/s10637-020-00891-9

    Article  CAS  Google Scholar 

  60. Gajria D, Gonzalez J, Feigin K, Patil S, Chen C, Theodoulou M, Drullinsky P, D’Andrea G, Lake D, Norton L, Hudis CA, Traina TA (2012) Phase II trial of a novel capecitabine dosing schedule in combination with lapatinib for the treatment of patients with HER2-positive metastatic breast cancer. Breast Cancer Res Treat 131:111–116. https://doi.org/10.1007/s10549-011-1749-y

    Article  CAS  PubMed  Google Scholar 

  61. Fisher B, Brown AM, Dimitrov NV, Poisson R, Redmond C, Margolese RG, Bowman D, Wolmark N, Wickerham DL, Kardinal CG et al (1990) Two months of doxorubicin-cyclophosphamide with and without interval reinduction therapy compared with 6 months of cyclophosphamide, methotrexate, and fluorouracil in positive-node breast cancer patients with tamoxifen-nonresponsive tumors: results from the National Surgical Adjuvant Breast and Bowel Project B-15. J Clin Oncol 8:1483–1496. https://doi.org/10.1200/jco.1990.8.9.1483

    Article  CAS  PubMed  Google Scholar 

  62. Levine MN, Bramwell VH, Pritchard KI, Norris BD, Shepherd LE, Abu-Zahra H, Findlay B, Warr D, Bowman D, Myles J, Arnold A, Vandenberg T, MacKenzie R, Robert J, Ottaway J, Burnell M, Williams CK, Tu D (1998) Randomized trial of intensive cyclophosphamide, epirubicin, and fluorouracil chemotherapy compared with cyclophosphamide, methotrexate, and fluorouracil in premenopausal women with node-positive breast cancer. National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 16:2651–2658. https://doi.org/10.1200/jco.1998.16.8.2651

    Article  CAS  PubMed  Google Scholar 

  63. Goldhirsch A, Colleoni M, Coates AS, Castiglione-Gertsch M, Gelber RD (1998) Adding adjuvant CMF chemotherapy to either radiotherapy or tamoxifen: are all CMFs alike? The International Breast Cancer Study Group (IBCSG). Ann Oncol 9:489–493. https://doi.org/10.1023/a:1008236502420

    Article  CAS  PubMed  Google Scholar 

  64. Wood WC, Budman DR, Korzun AH, Cooper MR, Younger J, Hart RD, Moore A, Ellerton JA, Norton L, Ferree CR (1994) Dose and dose intensity of adjuvant chemotherapy for stage II, node-positive breast carcinoma. N Engl J Med 330:1253–1259

    Article  CAS  PubMed  Google Scholar 

  65. Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, Grünwald V, Thompson JA, Figlin RA, Hollaender N (2010) Phase 3 trial of everolimus for metastatic renal cell carcinoma: final results and analysis of prognostic factors. Cancer 116:4256–4265

    Article  CAS  PubMed  Google Scholar 

  66. Finn RS, Martin M, Rugo HS, Jones SE, Im S-A, Gelmon KA, Harbeck N, Lipatov ON, Walshe JM, Moulder SL (2016) PALOMA-2: Primary results from a phase III trial of palbociclib (P) with letrozole (L) compared with letrozole alone in postmenopausal women with ER+/HER2–advanced breast cancer (ABC). J Clin Oncol 34(15):507–507

  67. Cristofanilli M, Turner NC, Bondarenko I, Ro J, Im S-A, Masuda N, Colleoni M, DeMichele A, Loi S, Verma S (2016) Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. Lancet Oncol 17:425–439

    Article  CAS  PubMed  Google Scholar 

  68. Finn RS, Crown JP, Lang I, Boer K, Bondarenko IM, Kulyk SO, Ettl J, Patel R, Pinter T, Schmidt M, Shparyk Y, Thummala AR, Voytko NL, Fowst C, Huang X, Kim ST, Randolph S, Slamon DJ (2015) The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol 16:25–35. https://doi.org/10.1016/s1470-2045(14)71159-3

    Article  CAS  PubMed  Google Scholar 

  69. Finn RS, Martin M, Rugo HS, Jones S, Im SA, Gelmon K, Harbeck N, Lipatov ON, Walshe JM, Moulder S, Gauthier E, Lu DR, Randolph S, Diéras V, Slamon DJ (2016) Palbociclib and letrozole in advanced breast cancer. N Engl J Med 375:1925–1936. https://doi.org/10.1056/NEJMoa1607303

    Article  CAS  PubMed  Google Scholar 

  70. Ettl J, Im SA, Ro J, Masuda N, Colleoni M, Schnell P, Bananis E, Lu DR, Cristofanilli M, Rugo HS, Finn RS (2020) Hematologic adverse events following palbociclib dose reduction in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: pooled analysis from randomized phase 2 and 3 studies. Breast Cancer Res 22:27. https://doi.org/10.1186/s13058-020-01263-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Masuda N, Mukai H, Inoue K, Rai Y, Ohno S, Mori Y, Hashigaki S, Muramatsu Y, Umeyama Y, Iwata H, Toi M (2019) Neutropenia management with palbociclib in Japanese patients with advanced breast cancer. Breast Cancer 26:637–650. https://doi.org/10.1007/s12282-019-00970-7

    Article  PubMed  Google Scholar 

  72. Hortobagyi G, Stemmer S, Burris H, Yap Y, Sonke G, Hart L, Campone M, Petrakova K, Winer E, Janni W (2021) Overall survival results from the phase III MONALEESA-2 trial of postmenopausal patients with HR+/HER2-advanced breast cancer treated with endocrine therapy±ribociclib. In: Presented at a global congress; September. p 21

  73. Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, Campone M, Blackwell KL, André F, Winer EP, Janni W, Verma S, Conte P, Arteaga CL, Cameron DA, Petrakova K, Hart LL, Villanueva C, Chan A, Jakobsen E, Nusch A, Burdaeva O, Grischke EM, Alba E, Wist E, Marschner N, Favret AM, Yardley D, Bachelot T, Tseng LM, Blau S, Xuan F, Souami F, Miller M, Germa C, Hirawat S, O’Shaughnessy J (2016) Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med 375:1738–1748. https://doi.org/10.1056/NEJMoa1609709

    Article  CAS  PubMed  Google Scholar 

  74. Beck J Ribociclib treatment benefit in patients with advanced breast cancer> 1 dose reduction: data from the MONALEESA-2,-3 and-7 trials. San Antonio Breast Cancer Symposium; December 4–8, 2018. In: Poster P6–18–06

  75. Tripathy D, Im SA, Colleoni M, Franke F, Bardia A, Harbeck N, Hurvitz SA, Chow L, Sohn J, Lee KS, Campos-Gomez S, Villanueva Vazquez R, Jung KH, Babu KG, Wheatley-Price P, De Laurentiis M, Im YH, Kuemmel S, El-Saghir N, Liu MC, Carlson G, Hughes G, Diaz-Padilla I, Germa C, Hirawat S, Lu YS (2018) Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial. Lancet Oncol 19:904–915. https://doi.org/10.1016/s1470-2045(18)30292-4

    Article  CAS  PubMed  Google Scholar 

  76. Sledge GW Jr, Toi M, Neven P, Sohn J, Inoue K, Pivot X, Burdaeva O, Okera M, Masuda N, Kaufman PA, Koh H, Grischke EM, Frenzel M, Lin Y, Barriga S, Smith IC, Bourayou N, Llombart-Cussac A (2017) MONARCH 2: abemaciclib in combination with fulvestrant in women with HR+/HER2- advanced breast cancer who had progressed while receiving endocrine therapy. J Clin Oncol 35:2875–2884. https://doi.org/10.1200/jco.2017.73.7585

    Article  CAS  PubMed  Google Scholar 

  77. Goetz MP, Toi M, Campone M, Sohn J, Paluch-Shimon S, Huober J, Park IH, Trédan O, Chen SC, Manso L, Freedman OC, Garnica Jaliffe G, Forrester T, Frenzel M, Barriga S, Smith IC, Bourayou N, Di Leo A (2017) MONARCH 3: abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol 35:3638–3646. https://doi.org/10.1200/jco.2017.75.6155

    Article  CAS  PubMed  Google Scholar 

  78. Dickler MN, Tolaney SM, Rugo HS, Cortés J, Diéras V, Patt D, Wildiers H, Hudis CA, O’Shaughnessy J, Zamora E, Yardley DA, Frenzel M, Koustenis A, Baselga J (2017) MONARCH 1, a phase II study of abemaciclib, a CDK4 and CDK6 inhibitor, as a single agent, in patients with refractory HR(+)/HER2(-) metastatic breast cancer. Clin Cancer Res 23:5218–5224. https://doi.org/10.1158/1078-0432.Ccr-17-0754

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Hamilton E, Cortes J, Ozyilkan O, Chen S-C, Petrakova K, Manikhas A, Jerusalem G, Hegg R, Huober J, Chapman SC (2021) nextMONARCH: abemaciclib monotherapy or combined with tamoxifen for metastatic breast cancer. Clin Breast Cancer 21(181–190):e182

    Google Scholar 

  80. Chan A, Delaloge S, Holmes FA, Moy B, Iwata H, Harvey VJ, Robert NJ, Silovski T, Gokmen E, Von Minckwitz G (2015) Neratinib after adjuvant chemotherapy and trastuzumab in HER2-positive early breast cancer: Primary analysis at 2 years of a phase 3, randomized, placebo-controlled trial (ExteNET). J Clin Oncol 33(15):508–508

  81. Saura C, Oliveira M, Feng YH, Dai MS, Chen SW, Hurvitz SA, Kim SB, Moy B, Delaloge S, Gradishar W, Masuda N, Palacova M, Trudeau ME, Mattson J, Yap YS, Hou MF, De Laurentiis M, Yeh YM, Chang HT, Yau T, Wildiers H, Haley B, Fagnani D, Lu YS, Crown J, Lin J, Takahashi M, Takano T, Yamaguchi M, Fujii T, Yao B, Bebchuk J, Keyvanjah K, Bryce R, Brufsky A (2020) Neratinib plus capecitabine versus lapatinib plus capecitabine in HER2-positive metastatic breast cancer previously treated with ≥ 2 HER2-directed regimens: phase III NALA trial. J Clin Oncol 38:3138–3149. https://doi.org/10.1200/jco.20.00147

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Bardia A, Mayer IA, Diamond JR, Moroose RL, Isakoff SJ, Starodub AN, Shah NC, O’Shaughnessy J, Kalinsky K, Guarino M (2017) Efficacy and safety of anti-trop-2 antibody drug conjugate sacituzumab govitecan (IMMU-132) in heavily pretreated patients with metastatic triple-negative breast cancer. J Clin Oncol 35:2141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Starodub AN, Ocean AJ, Shah MA, Guarino MJ, Picozzi VJ, Vahdat LT, Thomas SS, Govindan SV, Maliakal PP, Wegener WA (2015) First-in-human trial of a novel anti-Trop-2 antibody-SN-38 conjugate, sacituzumab govitecan, for the treatment of diverse metastatic solid tumors. Clin Cancer Res 21:3870–3878

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Bardia A, Tolaney S, Loirat D, Punie K, Oliveira M, Rugo H, Brufsky A, Kalinsky K, Cortés J, O’Shaughnessy J (2020) LBA17 ASCENT: a randomized phase III study of sacituzumab govitecan (SG) vs treatment of physician’s choice (TPC) in patients (pts) with previously treated metastatic triple-negative breast cancer (mTNBC). Ann Oncol 31:S1149–S1150

    Article  Google Scholar 

  85. Bardia A, Mayer IA, Vahdat LT, Tolaney SM, Isakoff SJ, Diamond JR, O’Shaughnessy J, Moroose RL, Santin AD, Abramson VG (2019) Sacituzumab govitecan-hziy in refractory metastatic triple-negative breast cancer. N Engl J Med 380:741–751

    Article  CAS  PubMed  Google Scholar 

  86. Bardia A, Hurvitz SA, Tolaney SM, Loirat D, Punie K, Oliveira M, Brufsky A, Sardesai SD, Kalinsky K, Zelnak AB, Weaver R, Traina T, Dalenc F, Aftimos P, Lynce F, Diab S, Cortés J, O’Shaughnessy J, Diéras V, Ferrario C, Schmid P, Carey LA, Gianni L, Piccart MJ, Loibl S, Goldenberg DM, Hong Q, Olivo MS, Itri LM, Rugo HS (2021) Sacituzumab govitecan in metastatic triple-negative breast cancer. N Engl J Med 384:1529–1541. https://doi.org/10.1056/NEJMoa2028485

    Article  CAS  PubMed  Google Scholar 

  87. Spring LM, Nakajima E, Hutchinson J, Viscosi E, Blouin G, Weekes C, Rugo H, Moy B, Bardia A (2021) Sacituzumab Govitecan for Metastatic Triple-Negative Breast Cancer: Clinical Overview and Management of Potential Toxicities. Oncologist 26:827–834

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Kalinsky K (2021) Outcomes in patients aged≥ 65 years in the phase 3 ASCENT study of sacituzumab govitecan in metastatic triple-negative breast cancer. J Clin Oncol 39(15):1011–1011

  89. Rugo HS, Tolaney SM, Loirat D, Punie K, Bardia A, Hurvitz SA, O’Shaughnessy J, Cortés J, Diéras V, Carey L (2021) Impact of UGT1A1 status on the safety profile of sacituzumab govitecan in the phase 3 ASCENT study in patients with metastatic triple-negative breast cancer. Cancer Res 81(4_Supplement): PS11-09

  90. Howell A, Robertson JF, Quaresma Albano J, Aschermannova A, Mauriac L, Kleeberg UR, Vergote I, Erikstein B, Webster A, Morris C (2002) Fulvestrant, formerly ICI 182,780, is as effective as anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment. J Clin Oncol 20:3396–3403

    Article  CAS  PubMed  Google Scholar 

  91. Osborne C, Pippen J, Jones S, Parker L, Ellis M, Come S, Gertler S, May J, Burton G, Dimery I (2002) Double-blind, randomized trial comparing the efficacy and tolerability of fulvestrant versus anastrozole in postmenopausal women with advanced breast cancer progressing on prior endocrine therapy: results of a North American trial. J Clin Oncol 20:3386–3395

    Article  CAS  PubMed  Google Scholar 

  92. Leo AD, Jerusalem G, Petruzelka L, Torres R, Bondarenko IN, Khasanov R, Verhoeven D, Pedrini JL, Smirnova I, Lichinitser MR (2014) Final overall survival: fulvestrant 500mg vs 250mg in the randomized CONFIRM trial. J Natl Cancer Inst 106:djt337

    Article  PubMed  Google Scholar 

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Funding

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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by ALL in coordination with PCDI patient advocates and Advisory Board members. The first draft of the manuscript was written by LG and ALL, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Lucy Gao.

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Competing interests

Lucy Gao: Affiliation with Massachusetts General Hospital. Aditya Bardia is a consultant/member of advisory board for Pfizer, Novartis, Genentech, Merck, Radius Health, Immunomedics/Gilead, Sanofi, Daiichi Pharma/Astra Zeneca, Phillips, Eli Lilly, and Foundation Medicine and receives contracted Research/Grant (to institution) from Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health, Immunomedics/Gilead, Daiichi Pharma/Astra Zeneca, and Eli Lilly. Mark E. Burkard is a member of Medical advisory board of Strata Oncology and receives research funding from Abbvie, Arcus, Apollomics, Elevation Oncology, Genentech, Loxo Oncology/Lilly, Puma, and Seagen. Kevin M. Kalinsky reports grants/contracts to his institution from Incyte, Novartis, Genentch, Eli Lilly, Pfizer, Calithera, Immunomedics, Acetylon, Seattle Genetics, Amgen, Zentalis, and CytomX Therapeutics; consulting fees/consultant honorarium from Daiichi Sankyo, Eli Lilly, Pfizer, Novartis, Eisai, AstraZeneca, Immunomedics, Merck, Seattle Genetics, Cyclocel, Oncosec, and 4D Pharma; speakers bureau: Eli Lilly; support for attending meetings and/or travel from Eli Lilly, AstraZeneca, and Pfizer; participation on advisory board (steering committee): Immunomedics, AstraZeneca, Ambryx, and Genentech; and stock options/employment: Grail (spouse), Array BioPharma (spouse), and Pfizer (spouse). Jeffrey Peppercorn reports spouse employment: GSK, Research funding Outcomes4me Inc—to institution, consulting Abbott Labs. Hope S. Rugo receives research support for clinical trials through the University of California: Pfizer, Merck, Novartis, Lilly, Roche, Daiichi, Seattle Genetics, Macrogenics, Sermonix, Boehringer Ingelheim, Polyphor, AstraZeneca, Ayala, Astellas, and Gilead; Honoraria from: Puma, Samsung, Mylan, Chugai, Blueprint, and NAPO; and Travel: GE Healthcare. Martha Carlson receives grant funding from Pfizer/NCCN and serves on a patient panel review for AstraZeneca. Maryam Lustberg is a consultant/member of advisory board for Pfizer, Lily, Astra Zeneca, Sanofi, and Novartis.

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Loeser, A.L., Gao, L., Bardia, A. et al. Patient-centered dosing: oncologists’ perspectives about treatment-related side effects and individualized dosing for patients with metastatic breast cancer (MBC). Breast Cancer Res Treat 196, 549–563 (2022). https://doi.org/10.1007/s10549-022-06755-5

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