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PET Protocol May Allow Neoadjuvant Chemo De-Escalation For HER2-Positive Early Breast Cancer

A pathological response-adapted imaging protocol might help identify early HER2-positive breast cancer patients who may not require chemotherapy alongside dual neoadjuvant HER2 blockade
26 May 2021
Anticancer Agents;  Breast Cancer;  Imaging

Author: By Lynda Williams, Senior medwireNews Reporter 


medwireNews: Initial phase II trial findings suggest that an 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET)-based pathological response-adapted protocol could be used to distinguish between HER2-positive early breast cancer patients who may and may not benefit from neoadjuvant chemotherapy. 

The European PHERGain study included women with stage I–IIIA operable breast cancer, all of whom had HER2-positive disease, and are being assessed for the co-primary endpoints of pathological complete response (pCR) and invasive disease-free survival, explain Javier Cortes, from the International Breast Cancer Center in Barcelona, Spain, and co-workers. 

For the study, 71 women were randomly assigned to receive six cycles of docetaxel plus carboplatin with trastuzumab and pertuzumab, followed by surgery 2–6 weeks after last dose (group A). 

¹⁸F-FDG-PET after the first two cycles of treatment showed a response in 61 (86%) of these patients, defined as a target lesion reduction from baseline of 40% or higher and no metabolic progression of non-target lesions. 

A further 285 patients (group B) were instead given two cycles of trastuzumab and pertuzumab, with letrozole or tamoxifen given to hormone receptor-positive postmenopausal and premenopausal patients, respectively.  

¹⁸F-FDG-PET scans demonstrated a response in 80% of patients and these 227 individuals were given a further six cycles of trastuzumab and pertuzumab before surgery, whereas the 58 nonresponders instead received six cycles of neoadjuvant docetaxel plus carboplatin with trastuzumab and pertuzumab before surgery. 

Overall, 89% of group A and 94% of group B patients underwent surgery. 

After a median 5.7 months of follow-up, the co-primary endpoint of pCR of invasive breast and axilla disease within 2 weeks of surgery and 6 weeks of completing neoadjuvant therapy in group B responders was met, with a rate of 37.9%, significantly greater than the historical rate. 

However, the rate of pCR was significantly higher in group A than group B overall (57.7 vs 35.4%). 

After adjusting for hormone receptor status, responders were more likely than nonresponders to achieve a pCR and this was true for both group A (65.6 vs 10.0%) and group B (37.9 vs 25.9%). 

Describing the pCR in nonresponders as “quite low” despite receipt of neoadjuvant chemotherapy, the team says this group “constitutes a target to investigate innovative and more personalised therapeutic strategies with other HER2-directed therapies currently in clinical development and other novel combinations”. 

Safety analysis revealed grade 3–4 adverse events in 59% of group A and 12% of group B, and serious adverse events in 29% and 5%, respectively.  

Chemotherapy was associated with grade 3–4 neutropenia, febrile neutropenia and diarrhoea, whereas diarrhoea was the most common symptom at this level in patients given only the dual HER2 blockade with or without endocrine therapy. 

In addition, group B was associated with significant and more favourable changes in global quality of life from baseline than group A, as well as in scores for nine of the 15 EORTC QLQ-C30 questionnaire measures. This was accompanied by a lower rate of health-related quality of life deterioration (35.5 vs 65.0%) that was particularly notable for the Group B responders (30.2%). 

Writing in The Lancet Oncology, Javier Cortes et al conclude: “Depending on the 3-year invasive disease-free survival results, this ¹⁸F-FDG-PET-based, pathological response-adapted strategy could provide useful information to identify patients who might not require chemotherapy.  

“Although such a strategy will require further clinical investigation, our study offers a potential future therapeutic option that enables an improvement in [health-related quality of life] for this patient population.” 



Pérez-García JM, Gebhart G, Ruiz Borrego M, et alChemotherapy de-escalation using an 18F-FDG-PET-based pathological response-adapted strategy in patients with HER2-positive early breast cancer (PHERGain): a multicentre, randomised, open-label, non-comparative, phase 2 trialLancet Oncol; Advance online publication 18 May 2021. DOI:10.1016/S1470-2045(21)00122-4

medwireNews (www.medwireNews.com) is an independent medical news service provided by Springer Healthcare. © 2021 Springer Healthcare part of the Springer Nature group

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