PHERGain study suggests some with HER2-positive early breast cancer may not need chemotherapy

The PHERGain trial, presented May 29 as part of the 2020 ASCO Annual Meeting, explored using PET scans to select people with early-stage HER2-positive breast cancer who may not need chemotherapy. The trial found that 40 percent of people with PET scans that showed cancer responding to targeted therapy early had no sign of cancer at surgery, without getting chemotherapy.

Background

Targeted therapies are an important part of HER2-positive breast cancer care, but for people with early-stage disease they are given with chemotherapy. Alongside new treatments have come new methods of providing and monitoring therapy, and researchers are seeking ways to better tailor treatment to your particular diagnosis, beyond broad categories like stage and subtype. This means using all treatments that are needed, but selecting when targeted therapy and surgery alone may reach a similar outcome to giving those treatments plus chemotherapy.

Neoadjuvant, or pre-surgery, therapy is one tool researchers use to provide tailored treatment. Giving medicine before surgery allows doctors to see its effect on the cancer. If the tumor dissolves completely, called a pathological complete response, the cancer is not likely to return. That person may not need as many additional treatments as they would if tumor tissue remained.

PHERGain was designed to see if imaging with positive emission tomography, also called a PET scan, could help find people with early-stage, HER2-positive breast cancer that responds well to targeted therapy without the need for chemotherapy.

Study design

The PHERGain trial had two groups, or arms, discussed at the 2020 ASCO Annual Meeting.

In the control arm, the group that got standard treatment, 71 people got chemotherapy then surgery and a year of the HER2-targeted therapies trastuzumab (Herceptin or biosimilar) and pertuzumab (Perjeta).

The study arm comprised 285 people who started on targeted therapy (trastuzumab and pertuzumab), but the course of treatment was decided by how the cancer responded. Participants in the study arm got a PET scan after two rounds of targeted therapy:

• People whose cancer responded to treatment stayed on targeted therapy until surgery.
• People whose cancer appeared not to respond got chemotherapy until surgery, and then a year of targeted therapy.

People who had responsive cancers and stayed on targeted therapy also had post-surgery treatment decided by whether any cancer remained at surgery.

• People who still had cancer got six cycles of chemotherapy and then four cycles of targeted therapy.
• People who had no cancer got 10 more cycles of targeted therapy.

Notably, participants whose cancer was found responsive at the PET scan and gone at the time of surgery never got chemotherapy.

Researchers reported early results at the ASCO Annual Meeting, showing how treatment decided by PET scan affected the chances that cancer was gone by surgery and whether women got lumpectomy. Over time, researchers will also look at how long participants go without breast cancer returning, but that data was not ready yet.

Results

After two cycles of trastuzumab and pertuzumab, PET scans showed that 79.6 percent of participants in the study arm had cancers that responded. These participants remained on targeted therapies until surgery. Of that group, 37.9 percent had no sign of cancer at surgery.

The high rate of pathological complete response confirms that PET scans can be used to predict who will have that outcome from trastuzumab and pertuzumab without chemotherapy.

People in the study arm, including both those who took targeted therapy and those who switched to chemotherapy, were somewhat less likely to get lumpectomy than those in the control arm, but the rates of lumpectomy were similar in the two groups:

• 59.2 percent of people in the control arm.
• 55.4 percent of people in the study arm.

Those who stayed on targeted therapy throughout the study were less likely to report side effects in general or to have ones that needed medical attention:

• 58.8 percent of people in the control arm needed medical attention for a side effect.
• 44.6 percent of people whose cancers did not show a response in the PET scan needed medical attention for a side effect.
• 1.3 percent of people whose cancer showed a response in PET scans (and got no chemotherapy) needed medical attention for a side effect

What this means for you

There are multiple HER2-targeted therapies available, but chemotherapy remains part of standard treatment, often given with two targeted therapies. The shift to pre-surgery treatment has opened up possibilities in breast cancer treatment to measure how well the cancer responds to medicine. These models do not allow everybody to drop chemotherapy from treatment, but the treatment recommended is better suited to your diagnosis. You can feel confident that you are getting enough treatment to increase the chances cancer won’t come back, but no more than you need.

PHERGain had encouraging early results, showing that the PET scan could identify people more likely to have cancer respond to targeted therapy. More information is needed on how many people actually go without cancer returning before this approach can be considered standard in cancer care. But even before final results are known, doctors are excited that this study is looking at sparing people from the effects of chemotherapy and designing ways to adapt treatment to cancer behavior.