Abstract 124P
Background
Preclinical synergy between IO and HER2-directed therapies has been reported. Currently, TCHP (docetaxel + carboplatin + trastuzumab + pertuzumab) regimen are used commonly with the highest pCR rate caused by double HER2 blockade (pCR rate: 60-70%). NCCN guideline recommend it as one of the preferred regimens for neoadjuvant therapy. Although toxicities are manageable, there are considerably higher G3/G4 AEs, including neutropenic fever, neurotoxicity, nephrotoxicity, emesis, and diarrhea. We hypothesized that TAHP without carboplatin but adding atezolizumab instead may have favorable toxicity profile compared with TCHP without compromising clinical outcomes in terms of pCR caused by synergistic effect of atezolizumab + THP.
Methods
Patients with HER2-positive stage II/III breast cancer whoreceiving neoadjuvant treatment were included. Eligible patients had any cT/N1–3/M0, or cT2-3/N0-1/M0; clinical stage IIA – IIIC, per AJCC 7th edition (patients with cT1mi/T1a/T1b/N0 are not eligible). Patients received 6 cycles of neoadjuvant TAHP. Primary end point was pCR rate. Secondary end points were response rate, invasive recurrent free survival, and toxicity.
Results
From May 2019 to May 2020, a total 67 patients were enrolled. The data cutoff was the end of Oct 2020, at which the last patient had received curative surgery. Among 67 patients, 32 were HR+. Median age was 52 (range 33-74). PD-L1 was positive by SP142 Ab in 13 patients (19.7%) at pre-treatment biopsy. Overall, pCR rate was 61.2% (41/67). Response rate was 94% (63/67). One patients could not receive surgery because of the progression during TAHP therapy. Neutropenia was found in 13 (19.4%), but neutropenic fever was found in 5 patients (7.5%). Rash was the most common immune-related toxicity (n=43, 64.2%, grade 3 in 1): encephalitis was found in 1 patient (G 3), immune-related hepatitis in 2 (G2 & G3), pneumonitis in 6 without G 3 or 4, and thyroid dysfunction in 6 patients. There was no treatment-related death.
Conclusions
Neoadjuvant TAHP regimen is a feasible and active treatment option in HER2-positive early breast cancer showing high pCR rate and modest toxicity.
Clinical trial identification
NCT03991878.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Roche, Dong A, Sanofi.
Disclosure
Y.H. Park: Non-Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Institutional, Research Grant, Contracted research: AstraZeneca; Non-Financial Interests, Institutional, Principal Investigator, Contracted research: AstraZeneca; Non-Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Institutional, Funding, Contracted research: Pfizer; Non-Financial Interests, Institutional, Principal Investigator, Contracted research: Pfizer; Non-Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Institutional, Research Grant, Contracted research: Roche; Non-Financial Interests, Institutional, Principal Investigator, Contracted research: Roche; Non-Financial Interests, Personal, Other, Medical writing support: Roche; Non-Financial Interests, Institutional, Principal Investigator, Contracted research: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Daiichi Sankto; Financial Interests, Personal, Advisory Board: Novartis; Non-Financial Interests, Institutional, Principal Investigator, Contracted research: Novartis; Non-Financial Interests, Personal, Advisory Board: Merck; Non-Financial Interests, Institutional, Principal Investigator, Contracted research: Merck; Financial Interests, Institutional, Research Grant, Contracted research: Merck; Financial Interests, Personal, Invited Speaker: Merck. S. Im: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: GSK; Financial Interests, Personal, Invited Speaker: Hanmi; Financial Interests, Personal, Invited Speaker: Eli-Lilly; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Roche; Non-Financial Interests, Personal, Advisory Board: AstraZeneca; Non-Financial Interests, Personal, Advisory Board: Eisai; Non-Financial Interests, Personal, Advisory Board: GSK; Non-Financial Interests, Personal, Advisory Board: Hanmi; Non-Financial Interests, Personal, Advisory Board: Eli-Lilly; Non-Financial Interests, Personal, Advisory Board: MSD; Non-Financial Interests, Personal, Advisory Board: Novartis; Non-Financial Interests, Personal, Advisory Board: Pfizer; Non-Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Institutional, Research Grant, Contracted research: AstraZeneca; Financial Interests, Institutional, Research Grant, Contracted research: Pfizer; Financial Interests, Institutional, Research Grant, Contracted research: Roche; Financial Interests, Institutional, Research Grant, Contracted research: Dae Woong; Financial Interests, Institutional, Research Grant, Contracted research: Eisai. H.K. Ahn: Non-Financial Interests, Personal, Advisory Board: Takeda; Non-Financial Interests, Personal, Advisory Board: BMS; Non-Financial Interests, Personal, Advisory Board: Roche; Non-Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Institutional, Research Grant, Contracted research: AstraZeneca; Financial Interests, Institutional, Research Grant, Contracted research: Roche; Financial Interests, Institutional, Research Grant, Contracted research: Beringer Ingelheim; Financial Interests, Institutional, Research Grant, Contracted research: MSD; Financial Interests, Institutional, Research Grant, Contracted research: Pfizer; Financial Interests, Institutional, Research Grant, Contracted research: Lilly. K. Lee: Non-Financial Interests, Personal, Invited Speaker: Roche; Non-Financial Interests, Personal, Invited Speaker: AstraZeneca; Non-Financial Interests, Personal, Advisory Board: Surface Oncology. J.H. Kim: Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: MSD; Non-Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Non-Financial Interests, Personal, Advisory Board: Eisai; Non-Financial Interests, Personal, Advisory Board: Bixink; Financial Interests, Institutional, Research Grant, Contracted research: Ono. K.S. Lee: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Institutional, Research Grant, Contracted research: Dong-A. J.H. Sohn: Financial Interests, Institutional, Research Grant, Contracted research: MSD; Financial Interests, Institutional, Research Grant, Contracted research: Roche; Financial Interests, Institutional, Research Grant, Contracted research: Novartis; Financial Interests, Institutional, Research Grant, Contracted research: AstraZeneca; Financial Interests, Institutional, Research Grant, Contracted research: Lilly; Financial Interests, Institutional, Research Grant, Contracted research: Pfizer; Financial Interests, Institutional, Research Grant, Contracted research: GSK; Financial Interests, Institutional, Research Grant, Contracted research: Daiichi Sankyo; Financial Interests, Institutional, Research Grant, Contracted research: Sanofi; Financial Interests, Institutional, Research Grant, Contracted research: Boehringer Ingelheim. K.H. Jung: Non-Financial Interests, Personal, Advisory Board: Roche; Non-Financial Interests, Personal, Advisory Board: AstraZeneca; Non-Financial Interests, Personal, Advisory Board: Novartis; Non-Financial Interests, Personal, Advisory Board: BiXink; Non-Financial Interests, Personal, Advisory Board: Takeda. All other authors have declared no conflicts of interest.