The following article features coverage from the American Society of Clinical Oncology 2020 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Results of a phase 2 trial provided early support for the use of 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT) imaging to identify patients with early-stage, HER2-positive breast cancer likely to benefit from less intensive treatment. These findings were presented during the ASCO20 Virtual Scientific Program.1

Although results of a previous phase 3 trial (KRISTINE trial; Identifier: NCT02131064) showed a pathological complete response (pCR) rate of 44.4% in patients with early-stage, HER2-positive breast cancer randomly assigned to receive dual HER2 blockade with trastuzumab plus pertuzumab, the pCR rate for patients in the study arm treated with both HER2-targeted agents plus chemotherapy was significantly higher at 55.7% (P =.016).2

Using a randomized, open-label, phase 2 trial (PHERGain; Identifier: NCT03161353) researchers sought to determine whether 18F-FDG-PET/CT could be used to identify patients with stage I-III, HER2-positive breast cancer who were candidates for dual HER2-targeted, chemotherapy-free treatment. 

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In this study, patients without evidence of metastatic disease on centrally reviewed baseline FDG-PET/CT imaging were randomly assigned in a 1:4 ratio to receive neoadjuvant therapy with trastuzumab and pertuzumab plus chemotherapy with docetaxel and carboplatin (cohort A) or trastuzumab and pertuzumab plus endocrine therapy with tamoxifen or letrozole for those with hormone receptor–positive disease (cohort B). Patients in cohorts A and B underwent randomization stratification by hormone receptor status.

Additional therapy was based on the findings of FDG-PET/CT imaging performed following 2 cycles of treatment in both patient cohorts. While those patients enrolled in cohort A continued with dual HER2 blockade plus chemotherapy for a total of 6 cycles, those enrolled in cohort B classified as PET responders (defined as showing at least a 40% reduction in SUVmax of 18F-FDG PET/CT compared with baseline) received an additional 6 cycles (8 cycles total of trastuzumab plus pertuzumab with or without endocrine therapy) whereas “PET non-responders” received 6 cycles of trastuzumab plus pertuzumab with added docetaxel plus carboplatin.

Following surgery, the PET responders in cohort B who did or did not achieve a pCR received 10 additional cycles of trastuzumab plus pertuzumab (with or without endocrine therapy depending on hormone receptor status) or 6 cycles of trastuzumab plus pertuzumab plus chemotherapy followed by 4 cycles of trastuzumab plus pertuzumab with or without endocrine therapy, respectively.

All patients in cohorts A and B completed 1 year of adjuvant trastuzumab plus pertuzumab with or without endocrine therapy, depending on hormone receptor status.

Those patients with subclinical evidence of metastases on baseline FDG-PET/CT imaging were included in a separate cohort (cohort C) and received 6 cycles of neoadjuvant therapy with pertuzumab, trastuzumab, docetaxel, and carboplatin. Following surgery or no surgery, these patients were treated with 12 cycles of dual HER2 blockade with or without endocrine therapy.

Coprimary endpoints of the study were pCR rate in PET responders and the 3-year rate of invasive disease-free survival (iDFS), both in cohort B.

Of the 356  patients included in the analysis, 71 and 285 patients were assigned to cohorts A and B, respectively. The median ages of patients in cohorts A and B were 51 years and 50 years, respectively, with node-positive disease and postmenopausal status a characteristic of approximately 50% of patients in each cohort.

The overall pCR rates in cohort A and B were 57.7% and 35.4% (P <.01), respectively. Nearly 80% of patients in cohort B were classified as PET responders, 37.9% of this subgroup of patients achieved a pCR and there was no significant difference in pCR rate according to hormone receptor status. In the remaining subgroup of PET nonresponders, the pCR rate was lower at 25.9%, although it did not differ significantly from that observed in PET responders (P =.069).

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Regarding safety, the frequency of grade 3 or higher adverse events was 58.8% for those in cohort A compared with 48.2% for PET nonresponders and 3.1% in PET responders in cohort B. Specifically, the frequencies of grade 3/4 febrile neutropenia were 20.6%, 17.9%, and 0% in these 3 respective groups.

In his concluding remarks, the presenting author, Javier Cortes, MD, PhD, head of breast cancer and gynecological cancers at Hospital Universitario Ramón y Cajal in Madrid, Spain stated  that “PET identifies patients with HER2-positive early breast cancer who are more likely to benefit from chemotherapy-free dual HER2-blockade with trastuzumab plus pertuzumab.  He further added that “follow-up is ongoing for the invasive iDFS end point. Depending on the results of this second co-primary end point, this strategy could select a group of HER2-positive, early-stage breast cancer patients who would not need chemotherapy.”

Disclosure: Research funding for this study was provided by F. Hoffmann-La Roche Ltd.

Read more of Cancer Therapy Advisor‘s coverage of the ASCO 2021 meeting by visiting the conference page.


  1. Cortes J, Gebhart G, Ruiz Borrego M, et al. Chemotherapy (CT) de-escalation using an FDG-PET/CT (F-PET) and pathological response-adapted strategy in HER2[+] early breast cancer (EBC): PHERGain Trial. Presented at: ASCO20 Virtual Scientific Program. J Clin Oncol. 2020;38(suppl):abstr 503.  
  2. Hurvitz SA, Martin M, Symmans WF, et al. Neoadjuvant trastuzumab, pertuzumab, and chemotherapy versus trastuzumab emtansine plus pertuzumab in patients with HER2-positive breast cancer (KRISTINE): a randomised, open-label, multicentre, phase 3 trial.  Lancet Oncol. 2018;19:115-126.