Safety and antitumor activity of pembrolizumab in patients with estrogen receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer

Clinical Cancer Research

Volumn 24, Issue 12, 2018, Pages 2804-2811

  Rugo, Hope S ^a   Delord, Jean Pierre ^b   Im, Seock Ah ^c   Ott, Patrick A ^d   Piha Paul, Sarina A ^e   Bedard, Philippe L ^f   Sachdev, Jasgit ^g   Le Tourneau, Christophe ^h   van Brummelen, Emilie M J ⁱ   Varga, Andrea ^j   Salgado, Roberto ^k   Loi, Sherene ^k   Saraf, Sanatan ^l   Pietrangelo, Dina ^l   Karantza, Vassiliki ^l   Tan, Antoinette R ^m,n  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b INSTITUT CLAUDIUS REGAUD   (France)

^c Seoul National University Hospital   (South Korea)

^d DANA FARBER CANCER INSTITUTE   (United States)

^e UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^f PRINCESS MARGARET HOSPITAL   (Canada)

^g HonorHealth and the Scottsdale Lincoln Health Network   (United States)

^h LABORATOIRE DES SCIENCES DU CLIMAT ET DE L ENVIRONNEMENT   (France)

ⁱ NETHERLANDS CANCER INSTITUTE   (Netherlands)

^j INSTITUT GUSTAVE ROUSSY   (France)

^k UNIVERSITY OF MELBOURNE   (Australia)

^l MERCK RESEARCH LABORATORIES   (United States)

^m RUTGERS CANCER INSTITUTE OF NEW JERSEY   (United States)

ⁿ LEVINE CANCER INSTITUTE   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

EPIDERMAL GROWTH FACTOR RECEPTOR 2; ESTROGEN RECEPTOR; PEMBROLIZUMAB; PROGRAMMED DEATH 1 LIGAND 1; CD274 PROTEIN, HUMAN; ERBB2 PROTEIN, HUMAN; IMMUNOLOGICAL ANTINEOPLASTIC AGENT; MONOCLONAL ANTIBODY; TUMOR MARKER;

ADULT; ADVANCED CANCER; AGED; ANTINEOPLASTIC ACTIVITY; ARTHRALGIA; ARTICLE; AUTOIMMUNE HEPATITIS; BRONCHITIS; CLINICAL ASSESSMENT; COHORT ANALYSIS; DECREASED APPETITE; DRUG RESPONSE; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; ESTROGEN RECEPTOR POSITIVE BREAST CANCER; FATIGUE; FEMALE; HUMAN; HUMAN TISSUE; INCIDENCE; MULTICENTER STUDY; MUSCLE WEAKNESS; NAUSEA; OPEN STUDY; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; PROTEIN EXPRESSION; PRURITUS; RASH; RESPONSE EVALUATION CRITERIA IN SOLID TUMORS; SEPTIC SHOCK; TREATMENT DURATION; TREATMENT OUTCOME; TUMOR ASSOCIATED LEUKOCYTE; BREAST TUMOR; CANCER GRADING; CANCER STAGING; CLINICAL TRIAL; DRUG EFFECT; IMMUNOLOGY; KAPLAN MEIER METHOD; METABOLISM; MIDDLE AGED; MORTALITY; PATHOLOGY;

ADULT; AGED; ANTIBODIES, MONOCLONAL, HUMANIZED; ANTINEOPLASTIC AGENTS, IMMUNOLOGICAL; B7-H1 ANTIGEN; BIOMARKERS, TUMOR; BREAST NEOPLASMS; FEMALE; HUMANS; KAPLAN-MEIER ESTIMATE; LYMPHOCYTES, TUMOR-INFILTRATING; MIDDLE AGED; NEOPLASM GRADING; NEOPLASM STAGING; RECEPTOR, ERBB-2; RECEPTORS, ESTROGEN;

EID: 85051820213     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-17-3452     Document Type: Article

References (40)

1. National Cancer Institute. SEER stat fact sheets: female breast cancer. 2017. Available at http://seer.cancer.gov/statfacts/html/breast.html. Accessed February 22, 2018.
2. Kennecke H, Yerushalmi R, Woods R, Cheang MC, Voduc D, Speers CH, et al. Metastatic behavior of breast cancer subtypes. J Clin Oncol 2010; 28:3271–7.
3. Senkus E, Cardoso F, Pagani O. Time for more optimism in metastatic breast cancer? Cancer Treat Rev 2014;40:220–8.
4. Carey LA, Perou CM, Livasy CA, Dressler LG, Cowan D, Conway K, et al. Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA 2006;295:2492–502.
5. Howell SJ, Howell A. Treatment of metastatic breast cancer: endocrine therapy. In: Harris JR, Lippman ME, Morrow M, Osborne CK, editors. Diseases of the Breast. 4th ed. Philadelphia, PA: Wolters Kluwer/Lippincott, Williams & Wilkins; 2010:856–76.
6. Finn RS, Crown JP, Ettl J, Schmidt M, Bondarenko IM, Lang I, et al. Efficacy and safety of palbociclib in combination with letrozole as first-line treatment of ER-positive, HER2-negative, advanced breast cancer: expanded analyses of subgroups from the randomized pivotal trial PALOMA-1/TRIO-18. Breast Cancer Res 2016;18:67.
7. Finn RS, Martin M, Rugo HS, Jones S, Im SA, Gelmon K, et al. Palbociclib and letrozole in advanced breast cancer. N Engl J Med 2016;375:1925–36.
8. Cristofanilli M, Turner NC, Bondarenko I, Ro J, Im SA, Masuda N, et al. 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 2016;17:425–39.
9. Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med 2016;375:1738–48.
10. Yamamoto-Ibusuki M, Arnedos M, Andre F. Targeted therapies for ER+/HER2-metastatic breast cancer. BMC Med 2015;13:137.
11. Black M, Barsoum IB, Truesdell P, Cotechini T, Macdonald-Goodfellow SK, Petroff M, et al. Activation of the PD-1/PD-L1 immune checkpoint confers tumor cell chemoresistance associated with increased metastasis. Onco-target 2016;7:10557–67.
12. Iwai Y, Hamanishi J, Chamoto K, Honjo T. Cancer immunotherapies targeting the PD-1 signaling pathway. J Biomed Sci 2017;24:26.
13. Patnaik A, Kang SP, Rasco D, Papadopoulos KP, Elassaiss-Schaap J, Beeram M, et al. Phase I study of pembrolizumab (MK-3475; anti-pd-1 monoclonal antibody) in patients with advanced solid tumors. Clin Cancer Res 2015;21:4286–93.
14. Ali HR, Glont SE, Blows FM, Provenzano E, Dawson SJ, Liu B, et al. PD-L1 protein expression in breast cancer is rare, enriched in basal-like tumours and associated with infiltrating lymphocytes. Ann Oncol 2015;26:1488–93.
15. Park IH, Kong SY, Ro JY, Kwon Y, Kang JH, Mo HJ, et al. Prognostic implications of tumor-infiltrating lymphocytes in association with programmed death ligand 1 expression in early-stage breast cancer. Clin Breast Cancer 2016;16:51–8.
16. Zhang Y, Morgan R, Chen C, Cai Y, Clark E, Khan WN, et al. Mammary-tumor-educated B cells acquire LAP/TGF-beta and PD-L1 expression and suppress anti-tumor immune responses. Int Immunol 2016;28: 423–33.
17. Janakiram M, Abadi YM, Sparano JA, Zang X. T cell coinhibition and immunotherapy in human breast cancer. Discov Med 2012;14:229–36.
18. Keytruda [prescribing information]. Whitehouse Station, NJ: Merck & Co., Inc.; 2017.
19. Chen R, Zinzani PL, Fanale MA, Armand P, Johnson NA, Brice P, et al. Phase II study of the efficacy and safety of pembrolizumab for relapsed/refractory classic hodgkin lymphoma. J Clin Oncol 2017;35:2125–32.
20. Seiwert TY, Burtness B, Mehra R, Weiss J, Berger R, Eder JP, et al. Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial. Lancet Oncol 2016;17:956–65.
21. 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. Lancet Oncol 2016;17:1497–508.
22. Herbst RS, Baas P, Kim DW, Felip E, Perez-Gracia JL, Han JY, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet 2016;387:1540–50.
23. 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. Lancet Oncol 2015;16:908–18.
24. Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med 2015;372:2521–32.
25. Nanda R, Chow LQ, 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;34:2460–7.
26. 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;35:1008.
27. Adams S, Loi S, Toppmeyer D, Cescon DW, Laurentiis MD, Nanda R, et al. Phase 2 study of pembrolizumab as first-line therapy for PD-L1–positive metastatic triple-negative breast cancer (mTNBC): preliminary data from KEYNOTE-086 cohort B. J Clin Oncol 2017;35:1088.
28. Roach C, Zhang N, Corigliano E, Jansson M, Toland G, Ponto G, et al. Development of a companion diagnostic PD-L1 immunohistochemistry assay for pembrolizumab therapy in non-small-cell lung cancer. Appl Immunohistochem Mol Morphol 2016;24:392–7.
29. Muro K, Chung HC, Shankaran V, Geva R, Catenacci D, Gupta S, et al. Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): a multicentre, open-label, phase 1b trial. Lancet Oncol 2016;17:717–26.
30. Salgado R, Denkert C, Demaria S, Sirtaine N, Klauschen F, Pruneri G, et al. The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Ann Oncol 2015;26:259–71.
31. 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 2016;13:228–41.
32. Romeu JL.Understanding binomial sequential testing, statistical confidence, reliability information analysis center (RIAC START). START selected topics in assurance related technologies 2016;12:1–8.
33. Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 2012;366:2443–54.
34. Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med 2015;372:2018–28.
35. Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 2015;373:23–34.
36. Vonderheide RH, Domchek SM, Clark AS. Immunotherapy for breast cancer: what are we missing? Clin Cancer Res 2017;23:2640–6.
37. 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: 40–50.
38. Dirix LY, Takacs I, Jerusalem G, Nikolinakos P, Arkenau HT, Forero-Torres A, et al. Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study. Breast Cancer Res Treat 2017.
39. Goel S, DeCristo MJ, Watt AC, BrinJones H, Sceneay J, Li BB, et al. CDK4/6 inhibition triggers anti-tumour immunity. Nature 2017;548: 471–5.
40. Yuan Y, Sudan N, Ebrahimi B, Yeon C, Upadhyaya G. Pembrolizumab, letrozole, and palbociclib in treating patients with stage IV estrogen receptor positive breast cancer with stable disease that has not responded to letrozole and palbociclib (NCT02778685). https://clinicaltrials.gov/ct2/show/study/NCT02778685. Accessed February 22, 2018.