Pharmacoeconomics of novel pharmacotherapies in triple-negative breast cancer

Figures & data

Table 1. Pivotal trials of novel pharmacotherapy options in early and advanced TNBC.

Trial (NCT identifier) and Reference	Setting	Population	Phase	No. of patients (randomization)	Experimental arm	Control arm	Primary end-points (key secondary)	Results	ESMO MCBS
IMpassion130 (NCT02425891) [17]	Metastatic	1 L mTNBC	III	451 (1:1)	Atezolizumab plus nab-paclitaxel	Nab-paclitaxel	PFS; OS	PFS: 7.2 vs. 5.5, HR 0.80, CI 95% 0.69 to 0.92; P = 0.002 (ITT); 7.5 vs. 5.0 months, HR 0.62, 95% CI 0.49 to 0.78; P < 0.001 (PD-L1 positive). OS: 21.0 vs. 18.7 months, HR 0.87, 95% CI 0.75, 1.02; P = 0.0770 (ITT); 25.4 vs. 17.9 months, HR 0.67, 95% CI 0.53, 0.86 [not formally tested per prespecified testing hierarchy] (PD-L1+)	3
IMpassion131 (NCT03125902) [18]	Metastatic	1 L mTNBC	III	651 (2:1)	Atezolizumab plus paclitaxel	Paclitaxel	PFS (OS)	PFS: 6.0 vs. 5.7 months, HR 0.82, 95% CI 0.60–1.12; P = 0.20 (PD-L1 positive) OS: 22.1 vs. 28.3 months, HR 1.11, 95% CI 0.76–1.64 (PD-L1 positive)	NA
KEYNOTE-355 (NCT02819518) [19]	Metastatic	1 L mTNBC	III	882 (2:1)	Pembrolizumab plus chemotherapy (nab-paclitaxel, paclitaxel, or gemcitabine – carboplatin)	Chemotherapy (nab-paclitaxel, paclitaxel, or gemcitabine – carboplatin)	PFS; OS	PFS: 9.7 vs. 5.6 months, HR 0.66, 95% CI, 0.50 to 0.88 (CPS-10); 7.6 vs. 5.6 months, HR 0.75; 95% CI, 0.62 to 0.91 (CPS-1) 7.5 vs. 5.6 months, 0.82; 95% CI, 0.70 to 0.98 (ITT) OS: 23.0 vs. 16.1, HR 0.73, 95% CI 0.55 to 0.95; P = 0.0185 (CPS-10) 17.6 vs. 16.0, HR 0.86, 95% CI 0.72 to 1.04; P = 0.1125 (CPS-1) 17.2 vs. 15.5 months, HR 0.89; 95% CI, 0.76 to 1.05 [significance not tested]	3
KEYNOTE-522 (NCT03036488) [20,21]	Early	Stage II or III TNBC	III	1174 (2:1)	Neoadjuvant Pembrolizumab plus paclitaxel and carboplatin, followed by pembrolizumab or placebo plus cyclophosphamide- either doxorubicin or epirubicin; pembrolizumab for 27 weeks after surgery	Neoadjuvant paclitaxel and carboplatin, followed by pembrolizumab or placebo plus cyclophosphamide- either doxorubicin or epirubicin	pCR; EFS	pCR (primary analysis): 64.8% vs. 51.2%; Δ 13.6%; 95% CI, 5.4 to 21.8; P < 0.001 EFS (at 36 months): 84.5% vs. 76.8%, HR 0.63, 95% CI, 0.48 to 0.82; P < 0.001	A
OlympiAD (NCT02000622) [22]	Metastatic	gBRCAm and HER2-negative mBC who had received ≤2 lines of chemotherapy for mBC	III	302 (2:1)	Olaparib	Capecitabine, vinorelbine, or eribulin	PFS (OS)	PFS: 7.0 vs. 4.2 months, HR 0.58, 95% CI 0.43 to 0.80; P < 0.001 OS: 19.3 vs. 17.1 months, HR 0.90, 95% CI 0.66 to 1.23, P = 0.513 [subgroup analysis] Prior treatments: 1 L HR 0.51, 95% CI 0.29 to 0.90; 2 L-3 L HR 1.13, 0.79 to 1.64 Hormone receptors status: TNBC HR 0.93, 0.62 to 1.43; HR + 0.86, 0.55 to 1.36 Prior platinum: yes: 0.83, 0.49 to 1.45; no: 0.91, 0.64 to 1.33	4
EMBRACA(NCT01945775) [23]	Metastatic	gBRCAm and HER2-negative mBC	III	431 (2:1)	Talazoparib	Capecitabine, eribulin, gemcitabine or vinorelbine	PFS (OS)	PFS: 8.6 vs. 5.6 months, HR 0.54, 95% CI 0.41 to 0.71; P < 0.001 OS: 19.3 vs. 19.5 months, HR 0.848, 95% CI 0.670 to 1.073, P = 0.17 [Subgroup analysis] Hormone receptor status: TNBC HR 0.899 (0.634 to 1.276); HR+ HR 0.827 (0.597 to 1.143)	4
OlympiA (NCT02032823) [24]	Early	gBRCAm and HER2-negative high-risk TNBC: T2 or higher or N1 or higher treated with adjuvant; not pCR treated with neoadjuvant HR+: N2 treated with adjuvant chemotherapy; not pCR and CPS+EG score of 3 or higher in neoadjuvant chemotherapy	III	1836 (1:1)	Adjuvant Olaparib for 52 weeks	Placebo	IDFS (DDFS; OS)	IDFS (at 4 years): 86.5% vs. 79.1%, HR 0.607 (0.476–0.771) [TNBC 87.3% vs 79.4%, HR 0.591 (0.450–0.772)] DDFS (at 4 years): 82.7% vs. 75.4%. HR 0.628, 95% CI 0.504–0.779 [TNBC 83.1% vs 75.2%, HR 0.620 (0.487–0.787)] OS (at 4 years): 89.8% vs. 86.4%, HR 0.678, 95% CI 0.503 to 0.907 [TNBC 90.1% vs. 86.3%, HR 0.640 (0.459–0.884)]	A
ASCENT (NCT02574455) [25]	Metastatic	Relapsed or refractory metastatic triple-negative breast cancer (all patients received previous taxanes)	III	529 (1:1)	Sacituzumab govitecan	Capecitabine, eribulin, gemcitabine, or vinorelbine	PFS (OS)	PFS: 5.6 vs. 1.7 months, HR 0.41, 95% CI, 0.32 to 0.52, P < 0.001 OS: 12.1 vs. 6.7 months, HR 0.48, 95% CI, 0.38 to 0.59, P < 0.001	4
DESTINY-Breast04 (NCT03734029) [26]	Metastatic	HER2-low mBC who had received one or two previous lines of chemotherapy	III	557 (2:1) [494 HR+, 63 HR-]	Trastuzumab deruxtecan	Capecitabine, eribulin, gemcitabine, nab-paclitaxel, paclitaxel	PFS (OS)	PFS: ITT: 9.9 vs. 5.1 months, HR 0.50; P < 0.001; TNBC: 8.5 vs. 2.9 months, HR 0.46; 95% CI, 0.24 to 0.89 OS: ITT: 23.4 vs. 16.8 months, HR 0.64, P = 0.001; TNBC: 18.2 vs. 8.3 months, HR 0.48, 95% CI, 0.24 to 0.95	4 (in the ITT)

Notes: Keys: ESMO MCBS, magnitude of clinical benefit scale of the European Society for Medical Oncology; Nr: number; 1 L: first-line; mTNBC: metastatic triple-negative breast cancer; PFS: progression-free survival; OS: overall survival; HR: hazard ratio; CI: confidence interval; ITT: intention to treat; PD-L1: programmed death-ligand 1; pCR: pathological complete response; EFS: event-free survival; gBRCAm: germinal BRCA-mutated; HR: hormone receptors; CPS: clinical-pathologic stage; EG: estrogen receptor status (E), grade (G); IDFS: invasive disease-free survival; DDFS: distant disease-free survival; mBC: metastatic breast cancer; NA: not applicable.

Table 2. Studies conducted to assess the pharmacoeconomic profile of novel pharmacotherapies in TNBC.

Study (Country)	Reference	Setting	Population	Drug	Control arm	Clinical data resource	Economic model structure	Life Years	QALY	ICER (WTP)	Cost-effective?
Wu et al. (U.S.)	[46]	Metastatic	A: PD-L1 status unknown B: PD-L1 positive	Atezolizumab + nab-paclitaxel	Nab-paclitaxel	IMpassion130 trial	Markov model	A: Δ 0.632; B: Δ 1.324	A: Δ 0.371; B: Δ 0.762	A: $281,448; B: $196,073 (WTP $200,000)	A: No; B: Yes
Li et al. (U.S)	[47]	Metastatic	A: ITT B: PD-L1 positive	Atezolizumab + nab-paclitaxel	Nab-paclitaxel	IMpassion130 trial	Markov model	Δ 0.24	Δ 0.16	A: $786,131; B: $361,218	No
Chisaki et al. (Japan)	[48]	Metastatic	PD-L1 positive	Atezolizumab + nab-paclitaxel	Nab-paclitaxel	IMpassion130 trial	Markov model	2.04 vs. 1.49	1.12 vs. 0.82	¥30,208,143/QALY (WTP ¥15,000,000)	No
Liu et al. (China)	[49]	Metastatic	A: ITT B: PD-L1 positive C: PD-L1 negative	Atezolizumab + nab-paclitaxel	Nab-paclitaxel	IMpassion130 trial	Partitioned survival model	A: 2.606 vs. 1.87; B: 3.101 vs. 1.836; C: 2.316 vs. 1.907	A: 1.724 vs. 1.297; B: 2.035 vs. 1.259; C: 1.548 vs. 1.34	A: $176,056/QALY B: $118,146/QALY C: $323,077/QALY	No
Weng et al. (China and U.S.)	[50]	Metastatic	A: ITT B: PD-L1 positive	Atezolizumab + nab-paclitaxel	Nab-paclitaxel	IMpassion130 trial	Markov model	A: 1.87 LYs vs. 1.29; B: 2.2 vs. 1.144	A: 1.41 vs. 0.99; B: 1.66 vs. 0.88	(U.S.) A: $331,996.89; B: US$229,359.88 (WTP $150,000/QALY) (China) A: $106,339.26; B: $72,971.88 (WTP $29,383/QALY)	No
Phua et al. (Singapore)	[51]	Metastatic	PD-L1 positive	Atezolizumab + nab-paclitaxel	Nab-paclitaxel	IMpassion130 trial	Partitioned-survival model	Δ 0.636	Δ 0.361	$324,550/QALY	No
Huang et al. (U.S)	[52]	Metastatic	PD-L1 positive	Pembrolizumab + chemotherapy (carboplatin + gemcitabine; or paclitaxel; or nab-paclitaxel)	Chemotherapy (carboplatin + vemcitabine; or paclitaxel; or nab-paclitaxel)	KEYNOTE-355	Partitioned-survival model	Δ 0.84	Δ 0.70	$182,732/QALY ($200,000)	Yes
Fasching et al. (US)	[53]	Early setting	High-risk early-stage (N+; and/or T2 or more)	Pembrolizumab + neoadjuvant chemotherapy (carboplatin + paclitaxel, followed by cyclophosphamide + epirubicin/doxorubicin) + adjuvant pembrolizumab for 27 weeks	Neoadjuvant chemotherapy (carboplatin + paclitaxel, followed by cyclophosphamide + epirubicin/doxorubicin)	KEYNOTE-522	Multistate transition model	Δ 3.37	Δ 2.90	$27,285/QALY	Yes
Saito et al. (Japan)	[54]	Metastatic	gBRCAm HER2-negative	Olaparib monotherapy with BRCA1/2 mutation profiling	Standard chemotherapy without BRCA1/2 mutation profiling (capecitabine; vinorelbine; eribulin)	OlympiAD trial	Markov model	Δ 0.040	Δ 0.037	$131,047/QALY ($89,286)	No
Olry de Labry Lima et al. (Spain)	[55]	Metastatic	gBRCAm HER2-negative A: patients pretreated with anthracyclines, taxanes and hormone therapy; B: patients pre-treated with capecitabine	A and B: Talazoparib	A: Capecitabine; B: Eribulin	EMBRACA trial	Partitioned survival model	Δ 0.35	Δ 0.23	A: 252,420.04€/QALY; B: 259,609.36€/QALY	No
Schwarz et al. (Germany)	[56]	Metastatic	gBRCAm HER2-negative	Talazoparib	Capecitabine, vinorelbine, gemcitabine, or eribuline	EMBRACA trial	Partitioned survival model	Δ 0.32	Δ 0.22	€323,932/QALY	No
Zettler et al. (US)	[57]	Early setting	Hypotetical 42-year-old women with BRCA-mutated, early-stage breast cancer	Olaparib	Placebo	OlympiA trial	Decision-analytic model (not specified)	Δ 1.21	Δ 1.15	$114,500/QALY ($150,000)	Yes
Chen et al. (China and U.S.)	[58]	Metastatic	mTNBC	Sacituzumab govitecan	Eribulin, vinorelbin, capecitabine, gemcitabine	ASCENT trial	Partitioned survival model [Markov model to validate the results]	Δ 0.41	Δ 0.35	Chinese perspective: ¥6375856/QALY [Markov Model ¥640,7626/QALY]; (WTP ¥72,447 to ¥217,341/QALY) U.S. perspective: $501123/QALY [Markov model $507,416/QALY]; (WTP $100,000 to $150,000/QALY)	No
Lang et al. (U.S.)	[59]	Metastatic	A: HER2-low mBC B: HER2-low HR+ mBC	Trastuzumab deruxtecan	Capecitabine, vinorelbine, gemcitabine, eribuline, paclitaxel, nab-paclitaxel	DESTINY-Breast04 trial	Partitioned survival model	/	Δ A: 0.451 Δ B: 0.470	A: [ICUR] $346,571.8/QALY B: [ICUR] $337,789.4/QALY (WTP $150,000/QALY)	No

Note: Keys: QALY: quality-adjusted life years; ICER: incremental cost-effectiveness ratio; WTP: willingness to pay; PD-L1: programmed death-ligand 1; ITT: intention to treat; mBC: metastatic breast cancer; ICUR: incremental cost–utility ratio.

Schmid P, Adams S, Rugo HS, et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med. 2018;379(22):2108–2121. DOI:10.1056/NEJMoa1809615

 PubMed Web of Science ®Google Scholar

Miles D, Gligorov J, André F, et al. Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer. Ann Oncol. 2021;32(8):994–1004. DOI:10.1016/j.annonc.2021.05.801

 PubMed Web of Science ®Google Scholar

Cortes J, Rugo HS, Cescon DW, et al. Pembrolizumab plus chemotherapy in advanced triple-negative breast cancer. N Engl J Med. 2022;387(3):217–226. DOI:10.1056/NEJMoa2202809

 PubMed Web of Science ®Google Scholar

Schmid P, Cortes J, Pusztai L, et al. Pembrolizumab for early triple-negative breast cancer. N Engl J Med. 2020;382(9):810–821. DOI:10.1056/NEJMoa1910549

 PubMed Web of Science ®Google Scholar

Schmid P, Cortes J, Dent R, et al. Event-free survival with pembrolizumab in early triple-negative breast cancer. N Engl J Med. 2022;386(6):556–567. DOI:10.1056/NEJMoa2112651

 PubMed Web of Science ®Google Scholar

Robson M, Im S-A, Senkus E, et al. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med. 2017;377(6):523–533. DOI:10.1056/NEJMoa1706450

 PubMed Web of Science ®Google Scholar

Litton JK, Rugo HS, Ettl J, et al. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N Engl J Med. 2018;379(8):753–763. DOI:10.1056/NEJMoa1802905

 PubMed Web of Science ®Google Scholar

Geyer CE, Garber JE, Gelber RD, et al. Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high-risk, early breast cancer. Ann Oncol. 2022;33(12):1250–1268. DOI:10.1016/j.annonc.2022.09.159

 PubMed Web of Science ®Google Scholar

Bardia A, Hurvitz SA, Tolaney SM, et al. Sacituzumab govitecan in metastatic triple-negative breast cancer. N Engl J Med. 2021;384(16):1529–1541. DOI:10.1056/NEJMoa2028485

 PubMed Web of Science ®Google Scholar

Modi S, Jacot W, Yamashita T, et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med. 2022;387(1):9–20. DOI:10.1056/NEJMoa2203690

 PubMed Web of Science ®Google Scholar

Wu B, Ma F. Cost-effectiveness of adding atezolizumab to first-line chemotherapy in patients with advanced triple-negative breast cancer. Ther Adv Med Oncol. 2020;12:175883592091600.

 Web of Science ®Google Scholar

Li J, Zhang T, Lu P, et al. Cost–effectiveness analysis of atezolizumab plus nab-paclitaxel for untreated metastatic triple-negative breast cancer. Immunotherapy. 2020;12(10):705–713. DOI:10.2217/imt-2020-0036

 PubMedGoogle Scholar

Chisaki Y, Kuwada Y, Matsumura C, et al. Cost-effectiveness analysis of atezolizumab plus nab-paclitaxel for advanced PD-L1 positive triple-negative breast cancer in Japan. Clin Drug Investig. 2021;41(4):381–389. DOI:10.1007/s40261-021-01017-6

 PubMedGoogle Scholar

Liu X, Lang Y, Liao Y, et al. Atezolizumab plus chemotherapy vs. chemotherapy in advanced or metastatic triple-negative breast cancer: a cost-effectiveness analysis. Front Public Health. 2021;9. DOI:10.3389/fpubh.2021.756899

 Google Scholar

Weng X, Huang X, Li H, et al. First-line treatment with atezolizumab plus nab-paclitaxel for advanced triple-negative breast cancer. Am J Clin Oncol. 2020;43(5):340–348. DOI:10.1097/COC.0000000000000671

 PubMed Web of Science ®Google Scholar

Phua LC, Lee SC, Ng K, et al. Cost-effectiveness analysis of atezolizumab in advanced triple-negative breast cancer. BMC Health Serv Res. 2020;20(1):581. DOI:10.1186/s12913-020-05445-6

 PubMed Web of Science ®Google Scholar

Huang M, Fasching P, Haiderali A, et al. Cost–effectiveness of pembrolizumab plus chemotherapy as first-line treatment in PD-L1-positive metastatic triple-negative breast cancer. Immunotherapy. 2022;14(13):1027–1041. DOI:10.2217/imt-2022-0082

 PubMedGoogle Scholar

Fasching PA, Huang M, Haiderali A, et al. 99P cost effectiveness of pembrolizumab in combination with chemotherapy as neoadjuvant therapy and continued as a single agent as adjuvant therapy for high-risk early-stage TNBC in the United States. Ann Oncol. 2022;33:S170–171.

 Google Scholar

Saito S, Nakazawa K, Nagahashi M, et al. Cost–effectiveness of BRCA1/2 mutation profiling to target olaparib use in patients with metastatic breast cancer. Per Med. 2019;16(6):439–448. DOI:10.2217/pme-2018-0141

 PubMed Web of Science ®Google Scholar

de Labry Lima AO, Špacírová Z, Fénix-Caballero S, et al. Cost-utility of talazoparib monotherapy treatment for locally advanced or metastatic breast cancer in Spain. Breast. 2021;58:27–33.

 PubMedGoogle Scholar

Schwarz F, Arefian H, Hartmann M, et al. Cost-effectiveness of talazoparib for patients with locally advanced or metastasized breast cancer in Germany. PLoS ONE. 2022;17(12):e0278460. DOI:10.1371/journal.pone.0278460

 PubMedGoogle Scholar

Zettler C, De Silva D, Blinder VS, et al. Cost effectiveness of adjuvant olaparib for BRCA-mutated, early-stage breast cancer. J Clin Oncol. 2022;40(16_suppl):6593. DOI:10.1200/JCO.2022.40.16_suppl.6593

 Google Scholar

Chen J, Han M, Liu A, et al. Economic evaluation of sacituzumab govitecan for the treatment of metastatic triple-negative breast cancer in China and the US. Front Oncol. 2021;11:11.

 Google Scholar

Lang Y, Wu B, Liu X. Economic evaluation of trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer in the United States. Breast Cancer: Target Therapy. 2022;14:453–463.

 PubMed Web of Science ®Google Scholar