A European trial has reported five years of results for patients with early breast cancer who never received chemotherapy. These patients had HER2-positive disease, a type driven by a protein called HER2. Their tumors shrank quickly on two targeted drugs alone, and in that group 92.4% were alive and free of invasive disease five years later1. The results of the trial, called PHERGain, were published in Nature Medicine1.
The headline number is strong, but the study has a limit that matters. It shows which patients might be spared chemotherapy. It does not formally prove that leaving chemotherapy out is as safe as giving it. Coverage of the paper notes that this proof is a question only a randomized trial can answer1.
What happened
PHERGain was a phase 2 trial, a mid-sized study that comes before the largest tests of a treatment. It ran in 45 hospitals across seven European countries1. It enrolled patients with HER2-positive breast cancer that could be removed by surgery, at stages I to IIIA, with tumors at least 1.5 cm across1.
The 356 patients were split unevenly. 71 went to a standard group that got chemotherapy, and 285 went to an experimental group1. The experimental group started on just two targeted drugs, trastuzumab (Herceptin) and pertuzumab (Perjeta), with no chemotherapy1. Some patients could also get hormone-blocking pills such as letrozole or tamoxifen, according to the trial’s registry record2.
After the typical patient had been followed for about 5.6 years, the experimental group’s results were as follows1:
- Among the 267 patients who had surgery as the plan required, 89.5% were free of invasive disease at five years1.
- 92.7% had no cancer spread to distant organs at five years1.
- In the subgroup that never got any chemotherapy, 92.4% were free of invasive disease at five years, and only one person had cancer spread to distant organs1. Coverage of the results puts that subgroup at 86 patients1.
The paper also reports long-term data from blood tests that pick up traces of tumor DNA in the bloodstream. These signals tracked with how well patients responded to treatment and how they did over time1.
How a scan decided who skipped chemo
The key feature of the trial is a check partway through treatment. After two cycles of the targeted drugs, each patient had a PET scan. This is an imaging test that tracks how much of a sugar-like tracer the tumor takes up. Cancer cells burn sugar faster than normal tissue, so a tumor that takes up less tracer is likely slowing down1. The trial counted a patient as responding if the tumor’s peak tracer uptake fell by at least 40%1.
Patients who met that bar kept going on the targeted drugs alone for six more cycles. Patients who did not were switched to chemotherapy plus the two targeted drugs, a built-in safety net1. At surgery, there was a second check. Patients who had responded on the scan but still had some cancer left received chemotherapy afterward1. Only those who passed both checks, meaning an early scan response and no cancer found at surgery (doctors call this a pathological complete response), finished treatment without any chemotherapy1.
The chemotherapy drugs listed in the trial record are docetaxel and carboplatin2. Drugs of these kinds can cause nerve damage in the hands and feet, tiredness, hair loss, low blood counts and heart harm1. The trial’s premise is that for tumors that respond very strongly to the targeted drugs, those side effects may be avoidable1.
What it does not show yet
PHERGain was described as randomized but non-comparative1. Patients were assigned to groups by chance, but the study was not built to test whether one group did better than the other. So the chemo-free patients were not compared head to head with similar patients who got chemo. That is why coverage stresses that the formal proof of safety still has to come from a randomized trial built for that question1.
Other limits are worth keeping in mind:
- The chemo-free subgroup is small, at 86 patients1.
- Patients who skipped chemo were, by design, those whose tumors responded best. Good outcomes in that group may partly reflect how favorable their cancers were to begin with.
- Five years is a meaningful stretch of follow-up, but some breast cancers come back later.
- The trial took place in Europe, and the sources reviewed here do not describe how the patients compare with the wider population of people with this cancer.
There is also a small difference in numbers between sources. The registry lists 377 people enrolled2, while the paper’s analysis describes 356 patients assigned to the two groups1. The sources reviewed do not explain the gap.
Who is behind it
The study was led by José Manuel Pérez-García, Javier Cortés, Antonio Llombart-Cussac and colleagues from MEDSIR, an international cancer research network based in Spain1. MedSIR is listed as the trial’s sponsor in the registry, which shows the study started on 26 June 2017 and is still active but no longer recruiting2. The sources reviewed here do not give further details on funding or on the authors’ ties to the makers of the drugs.
The same team published the trial’s three-year results in The Lancet in 20243. That earlier paper set out the study’s aim: to test whether a chemo-free plan built on the two targeted drugs was feasible, safe and effective, using the PET scan and surgery results to guide treatment3. The registry lists two main goals: the share of patients with no cancer left at surgery, and the share free of invasive disease at three years2. The new five-year report extends that follow-up.
How it fits the field
HER2-positive disease accounts for roughly 15 to 20% of breast cancers worldwide, an estimated 47,000 to 63,000 new cases a year in the United States1. Trastuzumab arrived in the late 1990s and turned an aggressive type of breast cancer into one that responds well to targeted treatment1. Pertuzumab, which latches onto a different part of the HER2 protein, later raised response rates further when added to it1.
Today, the usual approach for most patients with stage II or higher disease is both targeted drugs plus chemotherapy before surgery1. PHERGain tests a different idea. Instead of deciding on chemotherapy only from a patient’s risk before treatment, it makes the call mid-treatment, based on how the tumor actually responds1. Coverage of the paper describes this as a step beyond earlier, rougher attempts to cut back treatment1.
What to watch next
The main open question is whether a randomized trial built to compare chemo-free treatment directly against standard chemotherapy will confirm that some patients can safely skip it1. Also worth watching are the blood tests for tumor DNA. If they keep tracking outcomes, they could one day help doctors decide who needs chemotherapy alongside, or instead of, scans1. Finally, the registry shows the trial is still active2, so longer follow-up may show whether the results hold beyond five years.
Biohack reports research news. This article is not medical advice; treatment decisions belong with a patient’s care team.
