Tumor-Infiltrating Lymphocytes in Patients Receiving Trastuzumab/Pertuzumab-Based Chemotherapy: A TRYPHAENA Substudy

Ignatiadis, Michail; Eynden, Gert Van den; Salgado, Roberto; Fornili, Marco; Barèche, Yacine; Desmedt, Christine; Rothé, Françoise; Maetens, Marion; Venet, David; Holgado, Esther; McNally, Virginia; Kiermaier, Astrid; Savage, Heidi Hm; Wilson, Timothy R.; Cortés, Javier; Schneeweiß, Andreas; Willard-Gallo, Karen; Biganzoli, Elia; Sotiriou, Christos

doi:10.1093/jnci/djy076

Cited by 65 publications

(59 citation statements)

References 29 publications

(30 reference statements)

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“…We analyzed the relationship between TILs and clinicopathological characteristics. As reported in most literature, total TILs are not associated with age or tumor size in breast cancer patients [33,35,39,43,50]. Earlier published showed that there was major correlation between the expression of TILs and lymph node status [49,52], which was similar with our research.…”

Section: Correlation Of Tils With Clinicopathological Parameterssupporting

confidence: 91%

Predictive Value of Tumor Infiltrating Lymphocytes in Neoadjuvant Chemotherapy Treated Breast Cancer: A Meta-Analysis of 8052 Patients

Li¹,

Zhang²,

Wang³

et al. 2020

Preprint

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Background: We conducted a meta-analysis to determine the prognostic value of Tumor infiltrating lymphocytes (TILs) for patients with breast cancer on Neoadjuvant Chemotherapy, to explore the prognostic value of different TILs threshold in terms of pathological complete response (PCR).Methods: A systematic search of PubMed, EMBASE and Web of Science electronic databases was conducted to identify eligible articles published before September 2020. Data from studies were analyzed by using Review Manager 5.3 and Stata 15.0Results: A total of 22 published studies (including 8 052 patients) were eligible. Patients with high TILs level showed a higher rate of PCR to treatment (OR=3.182, 95 %CI, 2.549-3.973) compared to breast cancer patients with low TILs level. Although the association of TILs with response to neoadjuvant chemotherapy was similar across most breast cancer subtypes, there were a few differences ER negative or ER positive breast cancer. In studies (Type of breast cancer not clearly classified in the literature) where the cut-off value for TILs was ≥10 %, higher levels of total TILs predicted a higher PCR rate of Neoadjuvant Chemotherapy. However, for HER2-positive breast cancer patients, when a cut-off valve of TILs ≥ 30 % was used, the OR was 2.631 (95 % CI, 1.739-3.982, P = 0.000). TILs also were related to better DFS (HR=0.95, 95 %CI, 0.92-0.98, P=0.000) and overall survival (OS) (HR=0.90, 95 %CI, 0.85-0.95, P<0.0001) after Neoadjuvant Chemotherapy.Conclusions: TILs can be used as predictors of patients with breast cancer on Neoadjuvant Chemotherapy. TILs threshold with the greatest prognostic significance of PCR is as yet unknown, but a TILs threshold of at least 30 % is associated with the most powerful outcome prognostication of PCR.

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Section: Correlation Of Tils With Clinicopathological Parameterssupporting

confidence: 91%

Predictive Value of Tumor Infiltrating Lymphocytes in Neoadjuvant Chemotherapy Treated Breast Cancer: A Meta-Analysis of 8052 Patients

Li¹,

Zhang²,

Wang³

et al. 2020

Preprint

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“…e findings of Kim et al showed that discordance between IHC-based subtypes and PAM50-based intrinsic subtypes was related to inadequate treatment and diminished survival in BC [20]. Studies also indicated that the percentage of stromal tumor-infiltrating lymphocytes (TILs) was associated with a higher pCR rate and improved survival in patients with HER2 + BC [21][22][23]. e optimal predictive biomarkers need further validation to contribute to development of precision medicine.…”

Section: Introductionmentioning

confidence: 99%

Dual HER2 Blockade versus a Single Agent in Trastuzumab-Containing Regimens for HER2-Positive Early Breast Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

et al. 2020

Journal of Oncology

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Purpose. Although trastuzumab is the standard of care for patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC), drug resistance and disease relapse occur. erefore, we performed a meta-analysis to assess the efficacy and safety of trastuzumab-containing dual anti-HER2 therapy compared to trastuzumab alone. Methods. A systematic search was performed to identify eligible randomized controlled trials (RCTs). Main outcomes including event-free survival/invasive disease-free survival (EFS/iDFS), overall survival (OS), and safety were considered. Results. Ten RCTs were included (15,284 patients). Significant improvements were observed in both EFS/iDFS (HR 0.86, p � 0.0003) and OS (HR 0.86, p � 0.02) with trastuzumab-based dual anti-HER2 therapy, especially in adjuvant treatment, while in the neoadjuvant setting, dual-targeted therapy also achieved a substantial pathological complete response (pCR) benefit (HR 1.34, p � 0.0002). Subgroup analysis revealed that the EFS/iDFS benefit was slightly higher with trastuzumab plus pertuzumab or plus neratinib than trastuzumab plus lapatinib, while OS benefit was significant with trastuzumab plus lapatinib, but there were no subgroup differences (interaction test, p � 0.80 and 0.24, resp.). In addition, EFS/iDFS benefit was unrelated to hormone receptor status but pronounced in the lymph node-positive (LN+) subgroup, which should be interpreted cautiously for lacking interaction (p � 0.18). Besides, patients receiving dual therapy, especially with the lapatinib-containing regimen, experienced more toxicity, but no increase in cardiotoxicity. Conclusions. Despite being associated with more toxicity, trastuzumab-containing dual anti-HER2 therapy is superior to trastuzumab single agent for HER2-positive EBC independent of hormone receptor status. e correlation between survival and LN status needs further verification. Trastuzumab plus pertuzumab or plus neratinib is the preferred regimen with substantial efficacy and lower toxicity.

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“…We further explored the ability of CIRI to identify predictive biomarkers in the context of neoadjuvant chemotherapy for locally advanced HER2 + breast adenocarcinoma. We applied our CIRI-BRCA model to publicly available retrospective data from multiple clinical trials where neoadjuvant therapy was given (Esserman et al, 2012;Ignatiadis et al, 2019). We limited our analysis to only patients with HER2 + disease to examine the effect of dual HER2-targeted therapy with trastuzumab and pertuzumab.…”

Section: Comparison Of Ciri To Proportional-hazard Modelingmentioning

confidence: 99%

“…Therefore, we adapted our data-driven approach to deriving priors as used in CIRI to identify parameters related to therapeutic selection. In the case of CLL, this consisted of the therapies used in the CLL8, CLL10, and CLL11 dataset; for breast cancer, this consisted of neoadjuvant chemotherapy ± Trastuzumab as per the ISPY trial (Esserman et al, 2012), or neoadjuvant chemotherapy + Trastuzumab + Pertuzumab as per the TRYPHAENA trial (Ignatiadis et al, 2019). We used our previously established CIRI prognostic model priors for other shared covariates.…”

Section: Prediction Of Therapeutic Benefit In Subsets Of Patientsmentioning

confidence: 99%

“…In the case of CLL, this cross-validation framework was applied to patients from the CLL8, CLL10, and CLL11 trials (Eichhorst et al, 2016;Goede et al, 2014;Hallek et al, 2010), limiting our analysis to only patients with interim MRD assessment receiving immuno-chemotherapy. For breast cancer, we pooled patients from two clinical trials where neoadjuvant therapy was given (ISPY and TRYPHAENA) and where data was publicly available (Esserman et al, 2012;Ignatiadis et al, 2019). Here, we limited our analysis to HER2+ patients where survival data was available.…”

Section: Prediction Of Therapeutic Benefit In Subsets Of Patientsmentioning

confidence: 99%

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Dynamic Risk Profiling Using Serial Tumor Biomarkers for Personalized Outcome Prediction

Kurtz

Esfahani

Scherer

et al. 2019

Cell

157

114

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Tumor-Infiltrating Lymphocytes in Patients Receiving Trastuzumab/Pertuzumab-Based Chemotherapy: A TRYPHAENA Substudy

Abstract: Baseline TIL percentage provides independent prognostic information in patients treated with trastuzumab/pertuzumab-based neoadjuvant chemotherapy. However, further validation is required.

Cited by 65 publications

References 29 publications

Predictive Value of Tumor Infiltrating Lymphocytes in Neoadjuvant Chemotherapy Treated Breast Cancer: A Meta-Analysis of 8052 Patients

Predictive Value of Tumor Infiltrating Lymphocytes in Neoadjuvant Chemotherapy Treated Breast Cancer: A Meta-Analysis of 8052 Patients

Dual HER2 Blockade versus a Single Agent in Trastuzumab-Containing Regimens for HER2-Positive Early Breast Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Dynamic Risk Profiling Using Serial Tumor Biomarkers for Personalized Outcome Prediction

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