Clinical dilemma and systemic treatment strategy of triple-negative breast cancer in the elderly

doi:10.19401/j.cnki.1007-3639.2023.05.011

Abstract

Abstract:

There is no specific biomarker for triple-negative breast cancer (TNBC), and chemotherapy remains as backbone but with limited efficacy and more side effects. 10%-21% TNBC are elderly patients with high prevalence of concomitant cardio-cerebrovascular and renal complications, which may lead to intolerance of chemotherapy. How to properly treat these elderly TNBC patients becomes a big challenge during daily clinical practice. To date, few clinical trials specifically focus on elderly TNBC patients, thus no enough evidence-based safety and efficacy data are provided to support the proper therapy to this population. There are also challenges and controversies in the diagnosis and treatment. Elderly TNBC patients have special age-related disease characteristics and high non-cancer related mortality. Therefore, it is very important to balance survival benefit and quality of life during the treatment. This paper summarized data of the epidemiology, tumor biological behavior, current diagnosis and treatment status and the huge unmet medical needs of elderly TNBC patients, and explored the benefits of novel antibody-drug conjugate (ADC), to provide certain guidance on systemic treatment strategies for elderly TNBC patients.

Key words: Triple-negative breast cancer, Elderly patients, Systemic treatment, Antibody-drug conjugate

CLC Number:

R737.9

CHEN Junyao, ZHANG Wentao, LIU Qiao, NIE Jianyun. Clinical dilemma and systemic treatment strategy of triple-negative breast cancer in the elderly[J]. China Oncology, 2023, 33(5): 506-516.

Figures/Tables 2

Tab.1

Summary of studies related to treatment of advanced TNBC"

Study	Regimen	Line of therapy	Elderly patient n (%)	Primary endpoint result	TEAE (grade≥3)/%
CALG-B^[32]	Paclitaxel	≥1	≥65 years old: 272/1 048 (26%)	Objective response: 1st is 37% (95% CI: 33%-41%); 2nd is 24% (95% CI: 20%-29%)	Leucocytopenia (P=0.009 9), neutropenia (P=0.022), anorexia (P=0.028), increased bilirubin (P=0.003 5), neurotoxicity (P<0.000 1)
EMBRACE^[33][NCT00388726]	Eribulin vs TPC	≥2	Median age: 55 years old (27-85 years old)	OS: 13.1 months vs 10.6 months (HR=0.81,95% CI: 0.66-0.99, P=0.041); PFS: 3.7 months vs 2.2 months (HR=0.87, 95% CI: 0.71-1.05, P=0.137)	Neutropenia (45% vs 21%), leucopenia (14% vs 6%), asthenia/fatigue (9% vs 10%), peripheral neuropathy (8% vs 2%)
LOTUS^[34][NCT02162719]	Ipatasertib + paclitaxel vs placebo + paclitaxel	1	≥50 years old: 51/124 (41%)	PFS: 6.2 months vs 4.9 months (HR=0.60, 95% CI: 0.37-0.98, P=0.037)	54% vs 42%
IMpassion130^[35][NCT02425891]	Atezolizumab + nab-paclitaxel vs placebo + nab-paclitaxel	1	≥65 years old: 219/902 (24%)	PD-L1 + (immune cell expression≥1%) PFS: 7.5 months vs 5.3 months (HR=0.63, 95% CI: 0.50-0.80, P<0.000 1); PD-L1 + (immune cell expression≥1%) OS：25.4 months vs 17.9 months (HR=0.67, 95% CI: 0.53-0.86)	49% vs 43%
IMpassion131^[36][NCT03125902]	Atezolizumab + paclitaxel vs placebo + paclitaxel	1		PD-L1 + (immune cell expression≥1%) PFS: 6.0 months vs 5.7 months (HR=0.82, 95% CI: 0.60-1.12, P=0.20); PD-L1 + (immune cell expression≥1%) OS: 22.1 months vs 28.3 months (HR=1.11, 95% CI: 0.76-1.64)	53% vs 46%
KEYNOTE-355^[37][NCT02819518]	Pembrolizumab + TPC vs placebo + TPC	1	≥65 years old: 180/847 (21%)	PD-L1 + (combined positive score≥10) PFS: 9.7 months vs 5.6 months (HR=0.65, 95% CI: 0.49-0.86, P=0.001 2); PD-L1 + (combined positive score≥10) OS: 23.0 months vs 16.1 months (HR=0.73, 95% CI: 0.55-0.95, P=0.009 3)	68% vs 67%
OlympiAD^[38][NCT02000622]	Olaparib vs TPC	1-3	≥65 years old: 15/302 (5%)	TNBC PFS: 5.6 months vs 2.9 months (HR=0.43, 95% CI: 0.29-0.63); TNBC OS: 17.4 months vs 14.9 months (HR=0.93, 95% CI: 0.62-1.43)	38% vs 49.5%
EMBRACA^[39][NCT01945775]	Talazoparib vs TPC	1-4	≥65 years old: 37/431 (8%)	TNBC PFS: 5.8 months vs 2.9 months (HR=0.60, 95% CI: 0.41-0.87, P=0.075); OS:19.3 months vs 19.5 months (Whole population: HR=0.848, 95% CI: 0.55-1.06, P=0.17; TNBC: HR=0.899, 95% CI: 0.63-1.28)	55% vs 38%

Tab.1

Tab. 2

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Regimen	Line of therapy	elderly patients n (%)	Primary endpoint result	TEAE (grade≥3)/%
SG vs TPC^[56,60][NCT02574455]	3	≥65 years old: 44/235 (19%)	ORR: 35% vs 5%; (Elderly subgroup: 50% vs 0%）; PFS: 5.6 months vs 1.7 months (HR=0.39, 95% CI: 0.31-0.49, P<0.001); Elderly subgroup: 7.1 months vs 2.4 months (HR=0.22, 95% CI: 0.12-0.40); OS: 12.1 months vs 6.7 months (HR=0.48, 95% CI: 0.38-0.59, P<0.001); Elderly subgroup: 15.3 months vs 8.2 months (HR=0.37, 95% CI: 0.22-0.64)	64% vs 47%
T-DXd (DS-8201)^[61][NCT02564900]	7.5	Elderly proportion currently unknown, 7 (HER2 low-TNBC)	ORR: 14.3%	63% (neutropenia, interstitial pneumonia)
T-DXd (DS-8201)^[62][NCT04132960]	5	Elderly proportion currently unknown, 15 (HER2 low-TNBC)	ORR: 40%; PFS: 3.5 months; OS: 6.6 months
T-DXd (DS-8201) vs TPC^[50][NCT03734029]	3	Elderly proportion currently unknown, 40 (HER2 low-TNBC)	ORR: 50% vs 16.7%; PFS: 8.5 months vs 1.9 months （HR=0.46, 95% CI: 0.24-0.89); OS: 18.2 months vs 8.3 months (HR=0.48, 95% CI: 0.24~0.95)	52.6% vs 67.4% (fatal adverse events: pneumonia [2 patients (0.5%)] and ischemic colitis, disseminated intravascular coagulation, dyspnea, febrile neutropenia, and sepsis [1 patient each (0.3%)]
DS-1062^[58][NCT03401385]	3	Elderly proportion currently unknown, 44	ORR: 34%	45% (neutropenia, stomatitis)
RC-48^[59][NCT02881138, NCT03052634]	≥3 (25%)	Elderly proportion currently unknown, 2 (HER2 low-TNBC)	ORR: 39.6% (HER2 low, include HR+, TNBC); PFS: 5.7 months (HER2 low, include HR+，TNBC)	45.8% (neutropenia, hepatotoxicity, neurotoxicity)