Liều dùng tập trung vào bệnh nhân: Quan điểm của bác sĩ ung thư về tác dụng phụ liên quan đến điều trị và liều dùng cá nhân hóa cho bệnh nhân mắc ung thư vú di căn (MBC)

Springer Science and Business Media LLC - Tập 196 - Trang 549-563 - 2022
Anne L. Loeser1, Lucy Gao2, Aditya Bardia3, Mark E. Burkard4, Kevin M. Kalinsky5, Jeffrey Peppercorn, Hope S. Rugo6, Martha Carlson1, Janice Cowden1, Lesley Glenn1, Julia Maues1, Sheila McGlown1, Andy Ni7, Natalia Padron1, Maryam Lustberg8
1Patient-Centered Dosing Initiative, Salt Lake City, USA
2Yale School of Medicine, New Haven, USA
3Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, USA.
4University of Wisconsin Carbone Cancer Center, Madison, USA
5Winship Cancer Institute at Emory University, Atlanta, USA
6University of California San Francisco Comprehensive Cancer Center, San Francisco, USA
7Division of Biostatistics, Ohio State University, Columbus, USA
8Smilow Cancer Hospital/Yale Cancer Center, New Haven, USA

Tóm tắt

Mặc dù ung thư vú di căn (MBC) có thể điều trị, nhưng không thể chữa khỏi và hầu hết bệnh nhân cần điều trị liên tục. Trong khi các bác sĩ ung thư thường kê toa liều khởi đầu được khuyến nghị (RSD) theo nhãn được FDA phê duyệt, sự dung nạp của bệnh nhân có thể khác so với những gì được thấy trong các thử nghiệm lâm sàng. Chúng tôi báo cáo một khảo sát về quan điểm của các bác sĩ ung thư về độc tố liên quan đến điều trị và sự sẵn sàng thảo luận về liều dùng linh hoạt với bệnh nhân. Chúng tôi đã phát tán một khảo sát bí mật qua mạng xã hội/email vào mùa xuân năm 2021. Các người trả lời đủ điều kiện cần phải là bác sĩ ung thư có trụ sở tại Hoa Kỳ và có kinh nghiệm điều trị cho bệnh nhân mắc MBC. Trong số 131 người phản hồi, 119 người đủ điều kiện. Các bác sĩ ước tính rằng 47% bệnh nhân của họ báo cáo các tác dụng phụ liên quan đến điều trị gây distress; trong số đó, 15% đã đến phòng cấp cứu/bệnh viện và 37% đã bỏ lỡ việc điều trị. 74% (n = 87) bác sĩ cho biết triệu chứng của bệnh nhân đã cải thiện sau khi giảm liều. 87% (n = 104) cho biết họ đã từng, nếu thấy phù hợp, bắt đầu điều trị ở liều thấp hơn. Phần lớn (85%, n = 101) người trả lời không tin rằng RSD luôn hiệu quả hơn so với liều thấp hơn và 97% (n = 115) sẵn sàng thảo luận về liều dùng cá nhân hóa với bệnh nhân. Tác dụng phụ liên quan đến điều trị rất phổ biến ở bệnh nhân mắc MBC, dẫn đến việc bỏ lỡ điều trị và các cuộc thăm khám cấp cứu. Để giúp bệnh nhân dung nạp điều trị, các bác sĩ ung thư có thể giảm liều khởi đầu và/hoặc liều tiếp theo. Phần lớn các bác sĩ ung thư bác bỏ giả thuyết rằng liều cao hơn luôn là tốt hơn và sẵn sàng thảo luận về liều dùng cá nhân hóa với bệnh nhân. Với những cải thiện tiềm năng về chất lượng cuộc sống và chăm sóc lâm sàng, việc điều chỉnh liều nên trở thành một phần của quá trình ra quyết định chia sẻ thường xuyên giữa bệnh nhân và bác sĩ ung thư.

Từ khóa


Tài liệu tham khảo

Jones SE (2008) Metastatic breast cancer: the treatment challenge. Clin Breast Cancer 8:224–233 Minasian L, Rosen O, Auclair D, Rahman A, Pazdur R, Schilsky R (2014) Optimizing dosing of oncology drugs. Clin Pharmacol Ther 96:572–579 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 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 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 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 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 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 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 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 Ratain MJ (2014) Redefining the primary objective of phase I oncology trials. Nat Rev Clin Oncol 11:503–504 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 Norris DC (2017) Dose titration algorithm tuning (DTAT) should supersede ‘the’ maximum tolerated dose (MTD) in oncology dose-finding trials. F1000Research 6:112 Subbiah V, Kurzrock R (2018) Challenging standard-of-care paradigms in the precision oncology era. Trends Cancer 4:101–109 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 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 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 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 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 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 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 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 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 Project Optimus. FDA 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 Peck RW (2018) Precision medicine is not just genomics: the right dose for every patient. Annu Rev Pharmacol Toxicol 58:105–122 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 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 (2021) Amgen Provides Updated Information On LUMAKRAS™ (Sotorasib)1 Dose comparison study. In: PR Newswire, Thousand Oaks, CA (2020) About Us. In: Patient Centered Dosing Initiative 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 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 R Core Team (2020) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria 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 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 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 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 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 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 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 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 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 Breetvelt I, Van Dam F (1991) Underreporting by cancer patients: the case of response-shift. Soc Sci Med 32:981–987 (2014) Metastatic breast cancer landscape analysis: research report. MBC Alliance, New York, NY Markman M (2006) Chemotherapy-induced peripheral neuropathy: underreported and underappreciated. Curr Pain Headache Rep 10:275–278 Rao A, Cohen HJ (2004) Symptom management in the elderly cancer patient: fatigue, pain, and depression. JNCI Monogr 2004:150–157 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 Mathijssen RH, Sparreboom A, Verweij J (2014) Determining the optimal dose in the development of anticancer agents. Nat Rev Clin Oncol 11:272–281 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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