Around one-third of patients with early HER2-positive breast cancer can safely avoid chemotherapy via a PET-based, response-adapted treatment strategy, research findings indicate.

Analysis of data from the Phase II PHERGain study, published in The Lancet (link here) and funded by Roche, revealed an “excellent” 3-year invasive disease-free survival rate with the experimental approach, that was similar to that seen for chemotherapy-treated patients, researchers said.

In the study, patients with HER2-positive, stage I-IIIA invasive operable breast cancer from 45 hospitals in seven countries (Spain, France, Belgium, Germany, UK, Italy, and Portugal) were randomly allocated into one of two treatment arms:

• In Group A patients (n=71) received docetaxel, carboplatin, trastuzumab and pertuzumab (TCHP); and
• In Group B (n=285) patients received trastuzumab and pertuzumab with or without endocrine therapy, every 3 weeks.

Treatment in group B was administered according to PET results: PET-responders continued with trastuzumab and pertuzumab with or without endocrine therapy for six cycles, while PET-non-responders were switched to six cycles of TCHP.

Following surgery, PET-responders who failed to achieve a pathological complete response (pCR) were given six cycles of TCHP, and all patients completed up to 18 cycles of trastuzumab and pertuzumab.

Results showed that after a median follow-up of 43.3 months, the 3-year iDFS rate was 94.8% (95% CI 91·4–97·1; p=0·001) in group B and 98.3% in group A.

“Importantly, 85 (99%) of the 86 group B PET responder patients who reached a pCR and did not receive chemotherapy at any point of their treatment were free of breast cancer relapse at 3 years after surgery,” said Professor Helena Earl, Emeritus Professor of Clinical Cancer Medicine, University of Cambridge, in a linked editorial.

“These patients avoided all of the immediate, medium-term, and long-term toxicities of chemotherapy”.

The results also showed an estimated 3-year event-free survival rate of 98·4% in Group A and 93·5% in Group B, one death in group A (distant recurrent event) and four deaths in Group B (three distant recurrences events and one death by suicide), according to the paper.

On the safety side, treatment-related adverse events and serious adverse events (SAEs) were higher in patients in group A than in group B (grade ≥3: 62% vs 33%; SAEs: 28% vs 14%).

Key limitations of the study were its limited sample size and short follow-up, as well as the unavailability of trastuzumab emtansine for patients without pCR (which has become the adjuvant standard approach since the study), and that PET imaging is expensive with limited access.

However, the findings indicate that via a treatment strategy based on PET and adapted by pCR patients “can safely omit chemotherapy and receive exclusive dual HER2 blockade with trastuzumab and pertuzumab,” the authors concluded.

“Although such a strategy will require further clinical investigation and prolonged follow-up, our study offers a new therapeutic alternative to be considered in our daily clinical practice that enables a significant reduction of toxicity for this patient population without compromising efficacy,” they said.

According to Professor Earl, the trial “successfully optimised, and thereby personalised and de-escalated, treatment while preserving the same long-term outcomes for patients”.