Correlation between PIK3CA mutations in cell-free DNA and everolimus efficacy in HR+, HER2-advanced breast cancer: results from BOLERO-2.
BACKGROUND
The current analysis was performed to evaluate the impact of PIK3CA hotspot mutations on everolimus efficacy in BOLERO-2 participants, using cell-free DNA (cfDNA) from plasma samples collected at the time of patient randomisation.


METHODS
PIK3CA H1047R, E545K, and E542K mutations in plasma-derived cfDNA were analysed by droplet digital PCR (ddPCR). Median PFS was estimated for patient subgroups defined by PIK3CA mutations in each treatment arm.


RESULTS
Among 550 patients included in cfDNA analysis, median PFS in everolimus vs placebo arms was similar in patients with tumours that had wild-type or mutant PIK3CA (hazard ratio (HR), 0.43 and 0.37, respectively). Everolimus also prolonged median PFS in patients with PIK3CA H1047R (HR, 0.37) and E545K/E542K mutations (HR=0.30) with a similar magnitude.


CONCLUSIONS
Mutation analysis of plasma-derived cfDNA by ddPCR suggests that PFS benefit of everolimus was maintained irrespective of PIK3CA genotypes, consistent with the previous analysis of archival tumour DNA by next-generation sequencing.
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Mary Ellen
ME
Moynahan
Oncology Precision Medicine, Novartis Pharmaceuticals Corporation, East Hanover, NJ 07936, USA.
David
D
Chen
Oncology Precision Medicine, Novartis Pharmaceuticals Corporation, East Hanover, NJ 07936, USA.
Wei
W
He
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Patricia
P
Sung
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Aliaksandra
A
Samoila
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Daoqi
D
You
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Trusha
T
Bhatt
Oncology Precision Medicine, Novartis Pharmaceuticals Corporation, East Hanover, NJ 07936, USA.
Parul
P
Patel
Global Medical Affairs, Novartis Pharma AG, Basel CH-4002, Switzerland.
Francois
F
Ringeisen
Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Gabriel N
GN
Hortobagyi
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Jose
J
Baselga
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Sarat
S
Chandarlapaty
D000730:Androstadienes / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D002474:Cell-Free System; D058534:Class I Phosphatidylinositol 3-Kinases; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000097:blood* / Q000235:genetics*; D000068338:Everolimus / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D009154:Mutation / Q000235:genetics*; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D015996:Survival Rate
D000730:Androstadienes; D014408:Biomarkers, Tumor; D058534:Class I Phosphatidylinositol 3-Kinases; D004273:DNA, Neoplasm; D000068338:Everolimus; D019869:Phosphatidylinositol 3-Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C484760:PIK3CA protein, human; C508053:ERBB2 protein, human; C056516:exemestane