KEYNOTE-119: Phase III study of pembrolizumab (pembro) versus single-agent chemotherapy (chemo) for metastatic triple negative breast cancer (mTNBC)

Cortés, Javier; Lipatov, Oleg; Im, S-A; Gonçalvès, Anthony; Lee, K.S.; Schmid, Peter; Tamura, Keita; Testa, Laura; Witzel, I; Ohtani, S.; Zambelli, Stefania; Harbeck, Nadia; André, Fabrice; Dent, R; Zhou, Xiaoli; Karantza, Vassiliki; Mejia, Jamie; Winer, EP

doi:10.1093/annonc/mdz394.010

Cited by 117 publications

(125 citation statements)

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“…20 In support of this concept, the phase III KEYNOTE-119 trial (NCT02555657) in patients with pretreated mTNBC did not show an improvement in ORR, progression-free survival (PFS), or OS with single-agent pembrolizumab versus single-agent chemotherapy, although patients with the highest levels of tumor PD-L1 expression showed a trend toward greater benefit with pembrolizumab. 21 The PD-L1 inhibitors avelumab and atezolizumab have also been explored as ICI monotherapy in mTNBC. Avelumab demonstrated an ORR of 5.2% in 58 heavily pretreated patients in the phase Ib JAVELIN trial (NCT01772004), 22 and the phase I trial of atezolizumab (NCT01375842) led to an ORR of 10% in 115 pretreated patients, with no responses seen in the PD-L1-negative subgroup.…”

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confidence: 99%

Role of Immunotherapy in Triple-Negative Breast Cancer

Keenan

Tolaney

2020

Journal of the National Comprehensive Cancer Network

363

298

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Immune checkpoint inhibitors (ICIs) have led to durable clinical remissions in many metastatic cancers. However, the single-agent efficacy of ICIs in breast cancer is low, including in triple-negative breast cancer (TNBC), which has several key characteristics that enhance ICI responses. Strategies to improve anticancer immune responses in TNBC are urgently needed to extend survival for patients with metastatic disease. This review presents ICI monotherapy response rates and discusses combination strategies with chemotherapy, targeted therapies, and novel immunotherapies. It concludes with a summary of immunotherapy biomarkers in TNBC and a call to action for future directions of research critical to advancing the efficacy of immunotherapy for patients with TNBC.Although response rates to ICIs are higher in TNBC than in hormone receptor-positive and HER2-positive breast cancers, the single-agent efficacy is still low, with monotherapy response rates ranging from approximately 5% in

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confidence: 99%

Role of Immunotherapy in Triple-Negative Breast Cancer

Keenan

Tolaney

2020

Journal of the National Comprehensive Cancer Network

363

298

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“…However in a preplanned analysis according PD‐L1 expression (defined as % of PD‐L1 + CPS by the 22C3 assay), the performance of pembrolizumab improved in the 65% of the study population with CPS ≥ 1 (HR = 0.86; 95% CI 0.69‐1.106; P .0728), and it was further pronounced in the 33% of patients with CPS ≥ 10 (HR = 0.78; 95% CI 0.57‐1.06 P = .0574). This observation was more emphasized in an exploratory analysis of patients with CPS ≥ 20 (17% of the study population), in whom there was a real prolongation in the median OS in favor pembrolizumab vs chemotherapy (mOS 14.9 and 12.5 months, respectively, HR 0.58, 95% CI 0.38‐0.88), in addition to a meaningful increase in the ORR (26.3% and 11.5%, respectively) . Although this exploratory data seems quite rational, still it needs to be further confirmed in a prospective data set.…”

Section: Exploring Genetic Events To Tailor Therapy Of Mtnbcmentioning

confidence: 88%

“…In view of the limited treatment options in the second‐ or third‐line setting for mTNBC patients, the KEYNOTE‐119 phase trial III was subsequently designed to compare single‐agent pembrolizumab vs single‐agent chemotherapy (TPC) in these patients (n = 622). Unfortunately, the study did not meet any of its primary or secondary efficacy endpoints . In the ITT analysis the mOS was 9.9 and 10.8 months, respectively (HR = 0.97; 95% CI 0.82‐1.15).…”

Section: Exploring Genetic Events To Tailor Therapy Of Mtnbcmentioning

confidence: 98%

Personalized treatment in metastatic triple‐negative breast cancer: The outlook in 2020

et al. 2019

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Compared with other breast cancer subtypes, patients with triple‐negative breast cancer (TNBC), and irrespective to their disease stage, were always recognized to have the worst overall survival data. Although this does not seem different at the present time, yet the last few years have witnessed many breakthrough genomic and molecular findings, that could dramatically improve our understanding of the biological complexity of TNBC. Based on genomic analyses, it was consistently evident that TNBC comprises a heterogeneous group of cancers, which have numerous diverse molecular aberrations. This—in return—has provided a platform for a new generation of clinical trials using many innovative therapies, directed against such novel targets. At the present time, two PARP inhibitors and one anti‐PD‐L1 monoclonal antibody (in combination with chemotherapy) have been approved in certain subpopulations of metastatic TNBC (mTNBC) patients, which have finally brought this disease into the era of personalized medicine. In the current review, we will explore the genomic landscape of TNBC, through which many actionable targets were graduated. We will also discuss the results of the key—practice changing—clinical studies, and some upcoming personalized treatment options for patients with mTNBC, that may be clinically adopted in the near future.

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“…While longer follow-up needs to be awaited, pembrolizumab may eventually evolve as a clinically relevant addition to standard neoadjuvant therapy in TNBC. KEYNOTE-119, on the other hand, was a negative trial [3]. Overall, 622 patients with metastatic TNBC were randomized to receive pembrolizumab monotherapy or chemotherapy by investigator's choice (including capecitabine, eribulin, vinorelbine, and gemcitabine).…”

Section: Pembrolizumab In Triple-negative Breast Cancermentioning

confidence: 99%

ESMO 2019: breast cancer

Bartsch

2020

memo

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This articles reviews results of relevant breast cancer trials presented at the 2019 ESMO Meeting. In triple-negative disease, addition of pembrolizumab to standard neoadjuvant chemotherapy yielded a pathologic complete response (pCR) rate of 64.8%, the highest pCR rate reported to date in this setting; in addition, a trend towards improved eventfree survival was observed in the immunotherapy group. In pretreated patients with metastatic triplenegative breast cancer, single-agent pembrolizumab was not superior to conventional chemotherapy. In metastatic hormone-receptor positive disease, an update of the MONARCH2 and MonaLEEsa-3 studies indicated an overall-survival benefit in favour of the respective CDK4/6 inhibitor groups emphasizing the clinical importance of this class of drugs.

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KEYNOTE-119: Phase III study of pembrolizumab (pembro) versus single-agent chemotherapy (chemo) for metastatic triple negative breast cancer (mTNBC)

Cited by 117 publications

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Role of Immunotherapy in Triple-Negative Breast Cancer

Role of Immunotherapy in Triple-Negative Breast Cancer

Personalized treatment in metastatic triple‐negative breast cancer: The outlook in 2020

ESMO 2019: breast cancer

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