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Erschienen in: Current Oncology Reports 7/2018

01.07.2018 | Breast Cancer (B Overmoyer, Section Editor)

Checkpoint Inhibitors in the Treatment of Breast Cancer

verfasst von: Tomas G. Lyons, Maura N. Dickler, Elizabeth E. Comen

Erschienen in: Current Oncology Reports | Ausgabe 7/2018

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Abstract

Purpose of Review

The treatment landscape for many cancers has dramatically changed with the development of checkpoint inhibitors. This article will review the literature concerning the use of checkpoint inhibitors in breast cancer.

Recent Findings

The histological subtype of BC with the strongest signal of efficacy has been triple-negative breast cancer (TNBC). Early trials of single-agent checkpoint inhibitors did not demonstrate a uniformly positive signal. Clinical studies suggest response rates between 5 and 10% in pretreated patients and roughly 20–25% for untreated advanced TNBC. However, in the small subset of patients who do respond, the response is often durable. More encouraging results have been reported with their use in combination with chemotherapy in the neoadjuvant setting. Larger phase III studies are underway to confirm these earlier findings.

Summary

An immune-directed therapeutic approach for the management of BC is underway, and it is likely that combination therapy will be required to achieve a level of efficacy worthy of use in the BC treatment paradigm. These agents are not without both economic and clinical toxicity; therefore, it is imperative that we identify patients most likely to benefit from these therapies through well-designed biologically plausible clinical studies and by evaluating novel combinatorial approaches with informative biomarker driven correlative studies.
Literatur
1.
2.
Zurück zum Zitat DeSantis CE, Ma J, Goding Sauer A, Newman LA, Jemal A. Breast cancer statistics, 2017, racial disparity in mortality by state. CA Cancer J Clin. 2017;67(6):439–48.CrossRefPubMed DeSantis CE, Ma J, Goding Sauer A, Newman LA, Jemal A. Breast cancer statistics, 2017, racial disparity in mortality by state. CA Cancer J Clin. 2017;67(6):439–48.CrossRefPubMed
3.
Zurück zum Zitat Chen Daniel S, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 39(1):1–10. Chen Daniel S, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 39(1):1–10.
4.
Zurück zum Zitat Schumacher TN, Schreiber RD. Neoantigens in cancer immunotherapy. Science. 2015;348(6230):69–74.CrossRefPubMed Schumacher TN, Schreiber RD. Neoantigens in cancer immunotherapy. Science. 2015;348(6230):69–74.CrossRefPubMed
5.
Zurück zum Zitat Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA, Behjati S, Biankin AV, et al. Signatures of mutational processes in human cancer. Nature. 2013;500(7463):415–21.CrossRefPubMedPubMedCentral Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA, Behjati S, Biankin AV, et al. Signatures of mutational processes in human cancer. Nature. 2013;500(7463):415–21.CrossRefPubMedPubMedCentral
6.
Zurück zum Zitat Luen SJ, Salgado R, Fox S, Savas P, Eng-Wong J, Clark E, et al. Tumour-infiltrating lymphocytes in advanced HER2-positive breast cancer treated with pertuzumab or placebo in addition to trastuzumab and docetaxel: a retrospective analysis of the CLEOPATRA study. The Lancet Oncology. 2017;18(1):52–62.CrossRefPubMed Luen SJ, Salgado R, Fox S, Savas P, Eng-Wong J, Clark E, et al. Tumour-infiltrating lymphocytes in advanced HER2-positive breast cancer treated with pertuzumab or placebo in addition to trastuzumab and docetaxel: a retrospective analysis of the CLEOPATRA study. The Lancet Oncology. 2017;18(1):52–62.CrossRefPubMed
7.
Zurück zum Zitat Savas P, Salgado R, Denkert C, Sotiriou C, Darcy PK, Smyth MJ, et al. Clinical relevance of host immunity in breast cancer: from TILs to the clinic. Nat Rev Clin Oncol. 2015;13:228.CrossRefPubMed Savas P, Salgado R, Denkert C, Sotiriou C, Darcy PK, Smyth MJ, et al. Clinical relevance of host immunity in breast cancer: from TILs to the clinic. Nat Rev Clin Oncol. 2015;13:228.CrossRefPubMed
8.
Zurück zum Zitat Loi S, Michiels S, Salgado R, Sirtaine N, Jose V, Fumagalli D, et al. Tumor infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer: results from the FinHER trial. Ann Oncol : Off J Eur Soc Med Oncol. 2014;25(8):1544–50.CrossRef Loi S, Michiels S, Salgado R, Sirtaine N, Jose V, Fumagalli D, et al. Tumor infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer: results from the FinHER trial. Ann Oncol : Off J Eur Soc Med Oncol. 2014;25(8):1544–50.CrossRef
9.
Zurück zum Zitat Denkert C, von Minckwitz G, Darb-Esfahani S, Lederer B, Heppner BI, Weber KE, et al. Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy. Lancet Oncol. 2018;19(1):40–50.CrossRefPubMed Denkert C, von Minckwitz G, Darb-Esfahani S, Lederer B, Heppner BI, Weber KE, et al. Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy. Lancet Oncol. 2018;19(1):40–50.CrossRefPubMed
10.
Zurück zum Zitat Denkert C, Loibl S, Noske A, Roller M, Muller BM, Komor M, et al. Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer. J Clin Oncol : Off J Am Soc Clin Oncol. 2010;28(1):105–13.CrossRef Denkert C, Loibl S, Noske A, Roller M, Muller BM, Komor M, et al. Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer. J Clin Oncol : Off J Am Soc Clin Oncol. 2010;28(1):105–13.CrossRef
11.
Zurück zum Zitat Adams S, Gray RJ, Demaria S, Goldstein L, Perez EA, Shulman LN, et al. Prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancers from two phase III randomized adjuvant breast cancer trials: ECOG 2197 and ECOG 1199. J Clin Oncol. 2014;32(27):2959–66.CrossRefPubMedPubMedCentral Adams S, Gray RJ, Demaria S, Goldstein L, Perez EA, Shulman LN, et al. Prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancers from two phase III randomized adjuvant breast cancer trials: ECOG 2197 and ECOG 1199. J Clin Oncol. 2014;32(27):2959–66.CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Loi SDD, Adams S, et al. Pooled individual patient data analysis of stomal tumor infiltrating lymphocytes in primary triple negative breast cancer treated with anthracycline-based chemotherapy. San Antonio Breast Cancer Symp. 2015:S1–03. Loi SDD, Adams S, et al. Pooled individual patient data analysis of stomal tumor infiltrating lymphocytes in primary triple negative breast cancer treated with anthracycline-based chemotherapy. San Antonio Breast Cancer Symp. 2015:S1–03.
13.
Zurück zum Zitat Dieci MV, Mathieu MC, Guarneri V, Conte P, Delaloge S, Andre F, et al. Prognostic and predictive value of tumor-infiltrating lymphocytes in two phase III randomized adjuvant breast cancer trials. Ann Oncol : Off J Eur Soc Med Oncol. 2015;26(8):1698–704.CrossRef Dieci MV, Mathieu MC, Guarneri V, Conte P, Delaloge S, Andre F, et al. Prognostic and predictive value of tumor-infiltrating lymphocytes in two phase III randomized adjuvant breast cancer trials. Ann Oncol : Off J Eur Soc Med Oncol. 2015;26(8):1698–704.CrossRef
14.
Zurück zum Zitat Loi S, Adams S, Schmid P, Cortés J, Cescon DW, Winer EP, et al. Relationship between tumor infiltrating lymphocyte (TIL) levels and response to pembrolizumab (pembro) in metastatic triple-negative breast cancer (mTNBC): results from KEYNOTE-086. Ann Oncology. 2017;28(suppl_5). Loi S, Adams S, Schmid P, Cortés J, Cescon DW, Winer EP, et al. Relationship between tumor infiltrating lymphocyte (TIL) levels and response to pembrolizumab (pembro) in metastatic triple-negative breast cancer (mTNBC): results from KEYNOTE-086. Ann Oncology. 2017;28(suppl_5).
16.
Zurück zum Zitat Chambers CA, Kuhns MS, Egen JG, Allison JP. CTLA-4-mediated inhibition in regulation of T cell responses: mechanisms and manipulation in tumor immunotherapy. Annu Rev Immunol. 2001;19:565–94.CrossRefPubMed Chambers CA, Kuhns MS, Egen JG, Allison JP. CTLA-4-mediated inhibition in regulation of T cell responses: mechanisms and manipulation in tumor immunotherapy. Annu Rev Immunol. 2001;19:565–94.CrossRefPubMed
17.
Zurück zum Zitat Nanda R, Chow LQM, Dees EC, Berger R, Gupta S, Geva R, et al. Pembrolizumab in patients with advanced triple-negative breast cancer: phase Ib KEYNOTE-012 study. J Clin Oncol. 2016;34(21):2460–7.CrossRefPubMedPubMedCentral Nanda R, Chow LQM, Dees EC, Berger R, Gupta S, Geva R, et al. Pembrolizumab in patients with advanced triple-negative breast cancer: phase Ib KEYNOTE-012 study. J Clin Oncol. 2016;34(21):2460–7.CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat • Adams S, Schmid P, Rugo HS, Winer EP, Loirat D, Awada A, et al. Phase 2 study of pembrolizumab (pembro) monotherapy for previously treated metastatic triple-negative breast cancer (mTNBC): KEYNOTE-086 cohort A. J Clin Oncol. 2017;35(15_suppl):1008. This is the largest study evaluating a checkpoint inhibitor in advanced pretreated TNBC presented to date, showing a response rate of less than 5% in the total population. CrossRef • Adams S, Schmid P, Rugo HS, Winer EP, Loirat D, Awada A, et al. Phase 2 study of pembrolizumab (pembro) monotherapy for previously treated metastatic triple-negative breast cancer (mTNBC): KEYNOTE-086 cohort A. J Clin Oncol. 2017;35(15_suppl):1008. This is the largest study evaluating a checkpoint inhibitor in advanced pretreated TNBC presented to date, showing a response rate of less than 5% in the total population. CrossRef
19.
Zurück zum Zitat • Adams S LS, Toppmeyer DL, et al. KEYNOTE-086 cohort B: pembrolizumab monotherapy for PD-L1–positive, previously untreated, metastatic triple-negative breast cancer (mTNBC). San Antonio Breast Cancer Symposium 2017;Abstract PD6–10. This study investigated the checkpoint inhibitor pembrolizumab as a first-line therapy in PD-L1-positive advanced TNBC, showing a response rate of 23%. This response rate is less than standard taxane-based therapy as first-line therapy in TNBC. • Adams S LS, Toppmeyer DL, et al. KEYNOTE-086 cohort B: pembrolizumab monotherapy for PD-L1–positive, previously untreated, metastatic triple-negative breast cancer (mTNBC). San Antonio Breast Cancer Symposium 2017;Abstract PD6–10. This study investigated the checkpoint inhibitor pembrolizumab as a first-line therapy in PD-L1-positive advanced TNBC, showing a response rate of 23%. This response rate is less than standard taxane-based therapy as first-line therapy in TNBC.
20.
Zurück zum Zitat Rugo HS, Delord J-P, Im S-A, et al: Preliminary efficacy and safety of pembrolizumab (MK-3475) in patients with PD-L1–positive estrogen receptor–positive/HER2-negative advanced breast cancer enrolled in KEYNOTE-028. San Antonio Breast Cancer Symposium 2015; Abstract S5–07. Rugo HS, Delord J-P, Im S-A, et al: Preliminary efficacy and safety of pembrolizumab (MK-3475) in patients with PD-L1–positive estrogen receptor–positive/HER2-negative advanced breast cancer enrolled in KEYNOTE-028. San Antonio Breast Cancer Symposium 2015; Abstract S5–07.
21.
Zurück zum Zitat Loi S, Giobbie-Hurder A, Gombos A, et al. Phase Ib/II study evaluating safety and efficacy of pembrolizumab and trastuzumab in patients with trastuzumab-resistant HER2-positive advanced breast cancer: results from the PANACEA study (IBCSG 45-13/BIG 4-13/KEYNOTE-014). San Antonio Breast Cancer Symposium 2017; Abstract GS2–06. Loi S, Giobbie-Hurder A, Gombos A, et al. Phase Ib/II study evaluating safety and efficacy of pembrolizumab and trastuzumab in patients with trastuzumab-resistant HER2-positive advanced breast cancer: results from the PANACEA study (IBCSG 45-13/BIG 4-13/KEYNOTE-014). San Antonio Breast Cancer Symposium 2017; Abstract GS2–06.
22.
Zurück zum Zitat • Tolaney S, et al. (2017) Phase 1b/2 study to evaluate eribulin mesylate in combination with pembrolizumab in patients with metastatic triple-negative breast cancer. San Antonio Breast Cancer Symposium 2017; Abstract PD6–13. This study shows that checkpoint inhibition in combination with chemotherapy as first-line therapy for advanced TNBC appears to be safe with a response rate higher than historically reported for chemotherapy alone in this setting. Larger studies are ongoing in a hope to confirm these earlier findings. • Tolaney S, et al. (2017) Phase 1b/2 study to evaluate eribulin mesylate in combination with pembrolizumab in patients with metastatic triple-negative breast cancer. San Antonio Breast Cancer Symposium 2017; Abstract PD6–13. This study shows that checkpoint inhibition in combination with chemotherapy as first-line therapy for advanced TNBC appears to be safe with a response rate higher than historically reported for chemotherapy alone in this setting. Larger studies are ongoing in a hope to confirm these earlier findings.
23.
Zurück zum Zitat Schmid P, Park, YH, Munoz-Couselo, E, et al. Pembrolizumab + chemotherapy as neoadjuvant treatment for triple negative breast cancer (TNBC): preliminary results from KEYNOTE-173. J Clin Oncol 35, 2017 (suppl; abstr 556). Schmid P, Park, YH, Munoz-Couselo, E, et al. Pembrolizumab + chemotherapy as neoadjuvant treatment for triple negative breast cancer (TNBC): preliminary results from KEYNOTE-173. J Clin Oncol 35, 2017 (suppl; abstr 556).
24.
Zurück zum Zitat • Nanda R, Liu, MC, Yau, C, et al. Pembrolizumab plus standard neoadjuvant therapy for high risk breast cancer (BC): results from I-SPY 2. J Clin Oncol 35, 2017 (suppl; abstr 506). This adaptively designed neoadjuvant study demonstrated very encouraging results with pembrolizumab in combination with chemotherapy in TNBC. Larger confirmatory neoadjuvant studies are ongoing. • Nanda R, Liu, MC, Yau, C, et al. Pembrolizumab plus standard neoadjuvant therapy for high risk breast cancer (BC): results from I-SPY 2. J Clin Oncol 35, 2017 (suppl; abstr 506). This adaptively designed neoadjuvant study demonstrated very encouraging results with pembrolizumab in combination with chemotherapy in TNBC. Larger confirmatory neoadjuvant studies are ongoing.
25.
Zurück zum Zitat • Schmid P, Cruz, C, Braiteh, FS, et al. Atezolizumab in metastatic triple-negative breast cancer: long-term clinical outcomes and biomarker analyses. American Association for Cancer Research (AACR Annual Meeting) 2017; Abstract 2986. This study also demonstrated the low response rates (10%) for single-agent checkpoint inhibition with atezolizumab in advanced pretreated TNBC. However, a small subset of patients were shown to obtain durable responses. • Schmid P, Cruz, C, Braiteh, FS, et al. Atezolizumab in metastatic triple-negative breast cancer: long-term clinical outcomes and biomarker analyses. American Association for Cancer Research (AACR Annual Meeting) 2017; Abstract 2986. This study also demonstrated the low response rates (10%) for single-agent checkpoint inhibition with atezolizumab in advanced pretreated TNBC. However, a small subset of patients were shown to obtain durable responses.
26.
Zurück zum Zitat Adams S, Diamond, JR, Hamilton, EP, et al. Phase Ib trial of atezolizumab in combination with nab-paclitaxel in patients with metastatic triple-negative breast cancer (mTNBC). J Clin Oncol 34, 2016 (suppl; abstr 1009). Adams S, Diamond, JR, Hamilton, EP, et al. Phase Ib trial of atezolizumab in combination with nab-paclitaxel in patients with metastatic triple-negative breast cancer (mTNBC). J Clin Oncol 34, 2016 (suppl; abstr 1009).
27.
Zurück zum Zitat Dirix LY, Takacs I, Nikolinakos P, et al: Avelumab (MSB0010718C), an anti–PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase Ib JAVELIN solid tumor trial. San Antonio Breast Cancer Symposium 2015; Abstract S1–04. Dirix LY, Takacs I, Nikolinakos P, et al: Avelumab (MSB0010718C), an anti–PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase Ib JAVELIN solid tumor trial. San Antonio Breast Cancer Symposium 2015; Abstract S1–04.
28.
Zurück zum Zitat Litton JK, Rugo HS, Ettl J, et al. A phase 3 trial comparing talazoparib, an oral PARP inhibitor, to physician’s choice of therapy in patients with advanced breast cancer and a germline BRCA-mutation. San Antonio Breast Cancer Symposium 2017; Abstract GS6–07. Litton JK, Rugo HS, Ettl J, et al. A phase 3 trial comparing talazoparib, an oral PARP inhibitor, to physician’s choice of therapy in patients with advanced breast cancer and a germline BRCA-mutation. San Antonio Breast Cancer Symposium 2017; Abstract GS6–07.
29.
Zurück zum Zitat Ribas A, Puzanov I, Dummer R, Schadendorf D, Hamid O, Robert C, et al. Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial. The Lancet Oncology. 16(8):908–18. Ribas A, Puzanov I, Dummer R, Schadendorf D, Hamid O, Robert C, et al. Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial. The Lancet Oncology. 16(8):908–18.
30.
Zurück zum Zitat Herbst RS, Baas P, Kim D-W, Felip E, Pérez-Gracia JL, Han J-Y, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 387(10027):1540–50. Herbst RS, Baas P, Kim D-W, Felip E, Pérez-Gracia JL, Han J-Y, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 387(10027):1540–50.
31.
Zurück zum Zitat Langer CJ, Gadgeel SM, Borghaei H, Papadimitrakopoulou VA, Patnaik A, Powell SF, et al. Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study. The Lancet Oncology. 2016;17(11):1497–508.CrossRefPubMedPubMedCentral Langer CJ, Gadgeel SM, Borghaei H, Papadimitrakopoulou VA, Patnaik A, Powell SF, et al. Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study. The Lancet Oncology. 2016;17(11):1497–508.CrossRefPubMedPubMedCentral
32.
Zurück zum Zitat Rugo HS, Barry WT, Moreno-Aspitia A, et al. Long-term follow-up of CALGB 40502/NCCTG N063H (Alliance): a randomized phase III trial of weekly paclitaxel (P) compared to weekly nanoparticle albumin bound nab-Paclitaxel (NP) or ixabepilone (Ix) +/− bevacizumab as first-line therapy for locally recurrent or metastatic breast cancer (MBC). San Antonio Breast Cancer Symposium 2017; Abstract GS3–06. Rugo HS, Barry WT, Moreno-Aspitia A, et al. Long-term follow-up of CALGB 40502/NCCTG N063H (Alliance): a randomized phase III trial of weekly paclitaxel (P) compared to weekly nanoparticle albumin bound nab-Paclitaxel (NP) or ixabepilone (Ix) +/− bevacizumab as first-line therapy for locally recurrent or metastatic breast cancer (MBC). San Antonio Breast Cancer Symposium 2017; Abstract GS3–06.
33.
Zurück zum Zitat Robson M, Im S-A, Senkus E, Xu B, Domchek SM, Masuda N, et al. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med. 2017;377(6):523–33.CrossRefPubMed Robson M, Im S-A, Senkus E, Xu B, Domchek SM, Masuda N, et al. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med. 2017;377(6):523–33.CrossRefPubMed
34.
Zurück zum Zitat Lord CJ, Ashworth APARP. Inhibitors: synthetic lethality in the clinic. Science (New York, NY). 2017;355(6330):1152–8.CrossRef Lord CJ, Ashworth APARP. Inhibitors: synthetic lethality in the clinic. Science (New York, NY). 2017;355(6330):1152–8.CrossRef
35.
Zurück zum Zitat Domchek SM, Postel-Vinay S, Bang Y-J, et al. An open-label, multitumor, phase II basket study of olaparib and durvalumab (MEDIOLA): results in germline BRCA-mutated (gBRCAm) HER2-negative metastatic breast cancer (MBC). San Antonio Breast Cancer Symposium 2017; Abstract PD6–11. Domchek SM, Postel-Vinay S, Bang Y-J, et al. An open-label, multitumor, phase II basket study of olaparib and durvalumab (MEDIOLA): results in germline BRCA-mutated (gBRCAm) HER2-negative metastatic breast cancer (MBC). San Antonio Breast Cancer Symposium 2017; Abstract PD6–11.
37.
Zurück zum Zitat Adem C, Soderberg CL, Cunningham JM, Reynolds C, Sebo TJ, Thibodeau SN, et al. Microsatellite instability in hereditary and sporadic breast cancers. Int J Cancer. 2003;107:580–2.CrossRefPubMed Adem C, Soderberg CL, Cunningham JM, Reynolds C, Sebo TJ, Thibodeau SN, et al. Microsatellite instability in hereditary and sporadic breast cancers. Int J Cancer. 2003;107:580–2.CrossRefPubMed
38.
Zurück zum Zitat Anbazhagan R, Fujii H, Gabrielson E. Microsatellite instability is uncommon in breast cancer. Clin Cancer Res. 1999;5:839–44.PubMed Anbazhagan R, Fujii H, Gabrielson E. Microsatellite instability is uncommon in breast cancer. Clin Cancer Res. 1999;5:839–44.PubMed
39.
Zurück zum Zitat Toyama T, Iwase H, Yamashita H, Iwata H, Yamashita T, Ito K, et al. Microsatellite instability in sporadic human breast cancers. Int J Cancer. 1996;68:447–51.CrossRefPubMed Toyama T, Iwase H, Yamashita H, Iwata H, Yamashita T, Ito K, et al. Microsatellite instability in sporadic human breast cancers. Int J Cancer. 1996;68:447–51.CrossRefPubMed
40.
Zurück zum Zitat Middha S, Zhang L, Nafa K, Jayakumaran G, Wong D, Kim HR, et al. Reliable pan-cancer microsatellite instability assessment by using targeted next-generation sequencing data. JCO Precision Oncol. 2017;(1):1–17. Middha S, Zhang L, Nafa K, Jayakumaran G, Wong D, Kim HR, et al. Reliable pan-cancer microsatellite instability assessment by using targeted next-generation sequencing data. JCO Precision Oncol. 2017;(1):1–17.
41.
Zurück zum Zitat Bonneville R, Krook MA, Kautto EA, Miya J, Wing MR, Chen H-Z, et al. Landscape of microsatellite instability across 39 cancer types. JCO Precision Oncol. 2017;(1):1–15. Bonneville R, Krook MA, Kautto EA, Miya J, Wing MR, Chen H-Z, et al. Landscape of microsatellite instability across 39 cancer types. JCO Precision Oncol. 2017;(1):1–15.
42.
Zurück zum Zitat • https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/125514s014lbl.pdf. The FDA approval of pembrolizumab in MSI-H and/or dMMR cancers was based on data from 5 single-arm studies enrolling 149 patients of which 2 had BC. Although the incidence of MSI in BC is low at < 2%, it is important to consider the use of pembrolizumab in any BC patient, if the tumor is MSI-H. • https://​www.​accessdata.​fda.​gov/​drugsatfda_​docs/​label/​2017/​125514s014lbl.​pdf.​ The FDA approval of pembrolizumab in MSI-H and/or dMMR cancers was based on data from 5 single-arm studies enrolling 149 patients of which 2 had BC. Although the incidence of MSI in BC is low at < 2%, it is important to consider the use of pembrolizumab in any BC patient, if the tumor is MSI-H.
Metadaten
Titel
Checkpoint Inhibitors in the Treatment of Breast Cancer
verfasst von
Tomas G. Lyons
Maura N. Dickler
Elizabeth E. Comen
Publikationsdatum
01.07.2018
Verlag
Springer US
Erschienen in
Current Oncology Reports / Ausgabe 7/2018
Print ISSN: 1523-3790
Elektronische ISSN: 1534-6269
DOI
https://doi.org/10.1007/s11912-018-0701-2

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