178P - PD-L1 expression in ER-low versus triple-negative (TN) advanced breast cancer (aBC), and according to phenotypic evolution from primary to recurrent disease

Background

PD1/PD-L1 immune checkpoint inhibitors (ICIs), in association with chemotherapy, are available for the first-line treatment of TN aBC patients. Access to ICIs is restricted to patients with ER=0%/HER2- BC and PD-L1 positive (PD-L1+) status on either primary or recurrent BC. ER-low (ER=1-9%/HER2) aBC patients have currently no access to ICIs. Available evidence suggests that TNBC at relapse may either reflect a stable phenotype throughout the disease history or be the result of receptor loss from the primary tumor. PD-L1 positivity prevalence and dynamics according to ER expression levels and phenotypic evolution from primary to recurrent BC is currently unexplored.

Methods

Patients with TN (ER=0%/HER2-) or ER-low (ER=1-9%/HER2-) aBC phenotype were included. PD-L1 status was assessed on primary BC, recurrences or both using PD-L1 IHC 22C3 pharmDx assay and scored with the combined positive score (CPS). PD-L1+ status was defined as CPS≥10 (cutoff for pembrolizumab access in TN aBC).

Results

297 patients with ER<10%/HER2- aBC were included. Among TN aBC (n=231), 39.1%, 6.1% and 9.4% had ER+( ER≥10%)/HER2-, HER2+ and ER-low primary BC, respectively. Among ER-low aBC (66), 62.3%, 9.8% and 22.9% had ER+/HER2-, HER2+ and TN primary BC, respectively. PD-L1 status was available for 97 TN and 17 ER-low aBC cases. PD-L1+ rate was higher in metastases (38.1%) than primary tumor (27.0%). ER-low aBC, compared to TN, showed numerically higher PD-L1+ rate (47.1% vs 38.1%). According to primary BC phenotype, PD-L1+ rate was higher for ER-low > TN > ER+/HER2- > HER2+ (66.7% vs 42.4% vs 36% vs 22%). Among PD-L1-negative ER+/HER2-primary BC patients, 25% converted to PD-L1+ aBC.

Conclusions

ER-low aBC showed a substantial PD-L1 positivity rate thus emphasizing the therapeutic deprivation in terms of ICI access that these patients are currently facing. A not negligible proportion of non-TN primary BC patients exhibited PD-L1+ status, with a remarkable rate of PD-L1+ gain during disease evolution, thus further solidifying the notion that characterization of relapsing BC can play a major role in shaping treatment access for aBC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Ricerca Corrente 2023 - Istituto Oncologico Veneto IRCCS Padova.

Disclosure

F. Miglietta: Financial Interests, Personal, Invited Speaker: Roche, Novartis, Seagen, Pfizer, Lilli; Financial Interests, Personal, Advisory Board: AstraZeneca, MSD; Financial Interests, Personal, Writing Engagement: Menarini. T. Giarratano: Financial Interests, Personal, Invited Speaker, outside the submitted work: Roche, Novartis, Seagen, Eli Lilly, Gilead, Daiichi Sankyo. G. Griguolo: Financial Interests, Personal, Invited Speaker: Novartis, Eli Lilly, MSD; Financial Interests, Personal, Advisory Board: Gilead, Menarini, Seagen; Other, Travel Support: Novartis, Amgen, Daiichi Sankyo, Eli Lilly, Gilead; Other, Travel Support: Pfizer. C.A. Giorgi: Financial Interests, Personal, Invited Speaker, outside the submitted work: Eli Lilly, Novartis, Daiichi Sankyo, AstraZeneca, Seagen. F. Girardi: Financial Interests, Personal, Invited Speaker, outside the submitted work: AstraZeneca, Eli Lilly, Gilead. M. Fassan: Financial Interests, Institutional, Research Grant, outside the submitted work: Astellas, QED therapeutics, Macrophage pharma, Diaceutics; Financial Interests, Personal, Invited Speaker, outside the submitted work: Astellas Pharma, AstraZeneca, Pierre Fabre, GSK, Roche, Merck Sharp & Dohme, Johnson & Johnson, Bristol Myers Squibb, Amgen, Eli Lilly, Novartis, Incyte. V. Guarneri: Financial Interests, Personal, Invited Speaker: Eli Lilly, Novartis, GSK, AstraZeneca, Gilead, Exact Sciences; Financial Interests, Personal, Advisory Board: Eli Lilly, Novartis, MSD, Gilead, Eli Lilly, Merck Serono, Exact Sciences, Eisai, Olema Oncology, AstraZeneca, Daiichi Sankyo, Pfizer; Financial Interests, Institutional, Local PI: Eli Lilly, Roche, BMS, Novartis, AstraZeneca, MSD, Synton Biopharmaceuticals, Merck, GSK, Daiichi Sankyo, Nerviano, Pfizer; Non-Financial Interests, Member: ASCO. M.V. Dieci: Financial Interests, Personal, Advisory Board: Novartis, Eli Lilly, Seagen, Exact Science, Daiichi Sankyo, Gilead, reveal genomics; Financial Interests, Personal, Other, Consultancy: Pfizer; Financial Interests, Personal, Invited Speaker: Exact sciences, Gilead, Seagen, Daiichi Sankyo, Novartis, Eli Lilly; Financial Interests, Personal, Other, Consultancy on educational project: Roche. All other authors have declared no conflicts of interest.