Differences in sensitivity to new therapies between primary and metastatic breast cancer: A need to stratify the tumor response?

Abstract Objective We compared therapeutic response of Varlitinib + Capecitabine (VC) versus Lapatinib + Capecitabine (LC) in patients with human epidermal growth factor receptor 2‐positive metastatic breast cancer after trastuzumab therapy by assessing changes in target lesion (TL) diameter and vol...

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Main Authors: Hubert Beaumont, Nathalie Faye, Antoine Iannessi, Emmanuel Chamorey, Catherine Klifa, Chih‐Yi Hsieh
Format: Article
Language:English
Published: Wiley 2023-02-01
Series:Cancer Medicine
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Online Access:https://doi.org/10.1002/cam4.5236
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author Hubert Beaumont
Nathalie Faye
Antoine Iannessi
Emmanuel Chamorey
Catherine Klifa
Chih‐Yi Hsieh
author_facet Hubert Beaumont
Nathalie Faye
Antoine Iannessi
Emmanuel Chamorey
Catherine Klifa
Chih‐Yi Hsieh
author_sort Hubert Beaumont
collection DOAJ
description Abstract Objective We compared therapeutic response of Varlitinib + Capecitabine (VC) versus Lapatinib + Capecitabine (LC) in patients with human epidermal growth factor receptor 2‐positive metastatic breast cancer after trastuzumab therapy by assessing changes in target lesion (TL) diameter and volume per location. Methods We retrospectively analyzed the CT data of the ASLAN001‐003 study (NCT02338245). We analyzed TL size and number at each location focusing on therapeutic response from baseline to Week 12. We used TL diameter and volume to conduct an inter‐arm comparison of the response according to: RECIST 1.1; stratified per TL location and considering TLs independently. Multiple pairwise intra‐arm comparisons of therapeutic responses were performed. Considering TL independently, weighted models were designed by adding weighted mean TL responses grouped by location. Results We evaluated 42 patients (88 TL) and 35 patients (74 TL), respectively, at baseline and Week 12. We found reductions in breast TL burden in the VC arm compared to the LC arm (p = 0.002 (diameter), p < 0.001 (volume)). Responses and TL sizes at baseline were not correlated. Explained variabilities of volume change per TL location, patient and patient:TL interaction were 36%, 10% and 4% (VC), and 13%, 1% and 23%, (LC). A test of inter‐arm difference of responses yielded p = 0.07 (diameter), and p < 0.001 (volume). Conclusions The therapeutic responses differed across tumors' locations; the magnitude of the differences of responses across the tumors' locations were drug‐dependent. Stratified analysis of the response by tumor location improved drug comparisons and is a powerful tool to understand TL heterogeneity.
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spelling doaj-art-fa7098504ec84edd9305dabf24f34f2c2024-11-25T07:56:32ZengWileyCancer Medicine2045-76342023-02-011233112312210.1002/cam4.5236Differences in sensitivity to new therapies between primary and metastatic breast cancer: A need to stratify the tumor response?Hubert Beaumont0Nathalie Faye1Antoine Iannessi2Emmanuel Chamorey3Catherine Klifa4Chih‐Yi Hsieh5Median Technologies, Les Deux Arcs Valbonne FranceMedian Technologies, Les Deux Arcs Valbonne FranceCentre Antoine Lacassagne Nice FranceCentre Antoine Lacassagne Nice FranceMedian Technologies, Les Deux Arcs Valbonne FranceASLAN Pharmaceuticals Singapore SingaporeAbstract Objective We compared therapeutic response of Varlitinib + Capecitabine (VC) versus Lapatinib + Capecitabine (LC) in patients with human epidermal growth factor receptor 2‐positive metastatic breast cancer after trastuzumab therapy by assessing changes in target lesion (TL) diameter and volume per location. Methods We retrospectively analyzed the CT data of the ASLAN001‐003 study (NCT02338245). We analyzed TL size and number at each location focusing on therapeutic response from baseline to Week 12. We used TL diameter and volume to conduct an inter‐arm comparison of the response according to: RECIST 1.1; stratified per TL location and considering TLs independently. Multiple pairwise intra‐arm comparisons of therapeutic responses were performed. Considering TL independently, weighted models were designed by adding weighted mean TL responses grouped by location. Results We evaluated 42 patients (88 TL) and 35 patients (74 TL), respectively, at baseline and Week 12. We found reductions in breast TL burden in the VC arm compared to the LC arm (p = 0.002 (diameter), p < 0.001 (volume)). Responses and TL sizes at baseline were not correlated. Explained variabilities of volume change per TL location, patient and patient:TL interaction were 36%, 10% and 4% (VC), and 13%, 1% and 23%, (LC). A test of inter‐arm difference of responses yielded p = 0.07 (diameter), and p < 0.001 (volume). Conclusions The therapeutic responses differed across tumors' locations; the magnitude of the differences of responses across the tumors' locations were drug‐dependent. Stratified analysis of the response by tumor location improved drug comparisons and is a powerful tool to understand TL heterogeneity.https://doi.org/10.1002/cam4.5236biomarkersBreast NeoplasmsMultidetector Computed TomographyTumor burden
spellingShingle Hubert Beaumont
Nathalie Faye
Antoine Iannessi
Emmanuel Chamorey
Catherine Klifa
Chih‐Yi Hsieh
Differences in sensitivity to new therapies between primary and metastatic breast cancer: A need to stratify the tumor response?
Cancer Medicine
biomarkers
Breast Neoplasms
Multidetector Computed Tomography
Tumor burden
title Differences in sensitivity to new therapies between primary and metastatic breast cancer: A need to stratify the tumor response?
title_full Differences in sensitivity to new therapies between primary and metastatic breast cancer: A need to stratify the tumor response?
title_fullStr Differences in sensitivity to new therapies between primary and metastatic breast cancer: A need to stratify the tumor response?
title_full_unstemmed Differences in sensitivity to new therapies between primary and metastatic breast cancer: A need to stratify the tumor response?
title_short Differences in sensitivity to new therapies between primary and metastatic breast cancer: A need to stratify the tumor response?
title_sort differences in sensitivity to new therapies between primary and metastatic breast cancer a need to stratify the tumor response
topic biomarkers
Breast Neoplasms
Multidetector Computed Tomography
Tumor burden
url https://doi.org/10.1002/cam4.5236
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