2SPD-009 Analysis of olaparib and talazoparib as possible therapeutic alternatives in advanced breast cancer and a germline BRCA mutation

Camean-Castillo, M; Fenix-Caballero, S; Gil-Sierra,; Briceño-Casado, MP; Salmeron-Navas, FJ; Rey, EJ Alegre-Del; Rios-Sanchez, E; Diaz-Navarro, J; Martinez-Diaz, C; Borrero-Rubio, JM

doi:10.1136/ejhpharm-2019-eahpconf.49

Cited by 2 publications

(3 citation statements)

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“…The reason for this was that a previously conducted indirect comparative analysis following methodology outlined by Bucher, concluded that both drugs are equivalent. This was seen through the emergence of progression-free survival data that was statistically similar between treatment groups (HR 1.074; 95%CI 0.71–1.626) [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

“…Standard patients were assumed to have a standard weight of 70 Kg and a body height of 1.7 m 2 . In the case of talazoparib, price approval is still pending and, therefore, the current price for olaparib (for ovarian cancer) was taken as a reference as this is an alternative with a similar therapeutic value [ 13 ]. Finally, it was assumed that all patients who had terminal cancer ceased treatment one month earlier.…”

Section: Methodsmentioning

confidence: 99%

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Cost-utility of talazoparib monotherapy treatment for locally advanced or metastatic breast cancer in Spain

et al. 2021

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Breast cancer is one of the most frequent malignancies. The aim of the article is to analyse the cost-utility ratio and budgetary impact of talazoparib treatment for patients with locally advanced or metastatic gBRCA þ breast cancer from the perspective of the Spanish National Health System. Analyses were based on the EMBRACA clinical trial and the model was constructed according to "partitioned survival analysis". Two scenarios were considered in order to compare talazoparib with the alternatives of capecitabine, vinorelbine and eribulin: 1. Chemotherapy in patients pre-treated with anthracyclines/taxanes and, 2. A second-and subsequent-line treatment option. Treatment types following relapse were recorded in the mentioned clinical trial. The effectiveness measure used was quality-adjusted life years (QALY). The average health cost of patients treated at 43 months with talazoparib was 84,360.86V, whilst current treatment costs were 26,683.90V. The effectiveness of talazoparib was 1.93 years of survival (1.09 QALY) relative to 1.58 years (0.83 QALY) in the treatment group. The incremental cost-utility ratio was 252,420.04V/QALY. This represents the additional cost required to earn an additional QALY when changing from regular treatment to talazoparib. Regarding budgetary impact, the number of patients susceptible to receiving treatment with between 94 and 202 talazoparib was estimated, according to scenario and likelihood. The 3-year cost difference was between 6.9 and 9 million euros. The economic evaluation conducted shows an elevated incremental cost-utility ratio and budgetary impact. Taking these results into account, the price of talazoparib would have to be lower than that taken as a reference to reach the cost-utility thresholds.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Cost-utility of talazoparib monotherapy treatment for locally advanced or metastatic breast cancer in Spain

et al. 2021

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“…The lack of expression of oestrogen receptor, progesterone receptor and epidermal growth factor receptor 2 (HER2) makes TNBC di cult to treat leaving chemotherapy as the solely available option for most patients, both in early and advanced stages of the disease, despite its considerable side effects and limited success [3][4][5]. Nevertheless, thanks to of the continuous effort in searching molecularly targeted approaches for TNBC, the rst targeted therapies have been recently approved consisting in the PARP inhibitors Olaparib or Talazoparib [6], which is bene cial for BRCA-mutated patients, and the antiprogrammed cell death-ligand 1 (PD-L1) Atezolizumab plus nab-paclitaxel chemotherapy [7], which applies to patients with unresectable locally advanced or metastatic PD-L1-positive TNBCs.…”

Section: Introductionmentioning

confidence: 99%

Aptamer Targeted Therapy Potentiates Immune Checkpoint Blockade in Triple-Negative Breast Cancer

Camorani

Passariello

Agnello

et al. 2020

Preprint

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Background: Triple-negative breast cancer (TNBC) is a uniquely aggressive cancer with high rates of relapse due to resistance to chemotherapy, the current major option for treatment. TNBC expresses higher levels of programmed cell death-ligand 1 (PD-L1) compared to other breast cancers, providing the rationale for the recently approved immunotherapy with anti-PD-L1 monoclonal antibodies (mAbs). A huge effort is dedicated to identify actionable biomarkers that may allow for novel combination therapies with immune-checkpoint blockade in TNBC. Platelet-derived growth factor receptor β (PDGFRβ) is highly expressed in mesenchymal invasive TNBC, both on tumor cells and tumor microenvironment (TME). We recently proved that tumor growth and lung metastases are impaired in mouse models of human TNBC by a high efficacious PDGFRβ aptamer. Hence, we aimed at investigating the effectiveness of a novel combination treatment with the PDGFRβ aptamer and anti-PD-L1 mAbs in TNBC.Methods: The targeting ability of the anti-human PDGFRβ aptamer toward the murine receptor was verified by streptavidin-biotin assays and confocal microscopy, and its inhibitory function by transwell migration assays on PDGFRβ-positive cells. The anti-proliferative effects of the PDGFRβ aptamer/anti-PD-L1 mAbs combination was assessed in human MDA-MB-231 and murine 4T1 TNBC cells, both grown as monolayer or co-cultured with lymphocytes. Tumor cell lysis and cytokines secretion by lymphocytes were analyzed by LDH quantification and ELISA, respectively. Orthotopic 4T1 xenografts in syngeneic mice were used for dissecting the effect of aptamer/mAbs combination on tumor growth, metastasis and lymphocytes infiltration. Ex vivo analyses through immunohistochemistry, RT-qPCR and immunoblotting were performed. Results: We show that the PDGFRβ aptamer potentiates the anti-proliferative activity of anti-PD-L1 mAbs on both human and murine TNBC cells, according to its human/mouse cross-reactivity. Further, by binding to activated human and mouse lymphocytes, the aptamer enhances the anti-PD-L1 mAbs-induced cytotoxicity of lymphocytes against tumor cells. Importantly, the aptamer heightens the antibody efficacy in inhibiting tumor growth and lung metastases in a syngeneic mouse model by acting on both TME and cancer cells. Conclusion: Co-treatment of PDGFRβ aptamer with anti-PD-L1 mAbs is a viable strategy, thus providing for the first an evidence of the efficacy of PDGFRβ/PD-L1 co-targeting combination therapy in TNBC.

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2SPD-009 Analysis of olaparib and talazoparib as possible therapeutic alternatives in advanced breast cancer and a germline BRCA mutation

Cited by 2 publications

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Cost-utility of talazoparib monotherapy treatment for locally advanced or metastatic breast cancer in Spain

Cost-utility of talazoparib monotherapy treatment for locally advanced or metastatic breast cancer in Spain

Aptamer Targeted Therapy Potentiates Immune Checkpoint Blockade in Triple-Negative Breast Cancer

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