A phase 3 clinical trial has shown that adding a targeted immunotherapy drug to chemotherapy dramatically improved – almost doubled – the cure rate for patients with the most common kind of breast cancer. The findings suggest adopting a new treatment paradigm for the disease.
A couple of years ago, New Atlas covered how treating Hodgkin lymphoma, a cancer of the lymphatic system, by combining an immunotherapy drug with chemotherapy led to greatly improved remission rates compared to those who received chemotherapy alone.
Now, the recently published results of an international phase 3 clinical trial led by Australia’s Peter MacCallum Cancer Center (Peter Mac) have shown that using the same kind of treatment combination is also effective against the most common kind of breast cancer.
Globally, in 2020, over 2.3 million new cases of breast cancer were diagnosed, of which 70% were a subtype known as estrogen receptor-positive (ER+) and human epidermal growth factor receptor 2-negative (HER2–). Cancer cells that are ER+ have receptors that can receive signals from estrogen hormones. When these receptors are activated, it can promote the growth of cancer cells. HER2– cancer cells don’t have an excess of HER2 receptors, generally making them less aggressive and slower-growing.
The response of ER+/HER2– breast cancer to treatment varies widely, which not only affects clinical outcomes but can pose a challenge to the effective medical management of the condition. Current treatments for high-risk, early-stage ER+/HER2– breast cancer include chemotherapy followed by surgery (called neoadjuvant therapy) or prolonged hormone therapy to stop the effect of estrogen on breast cancer cells, with or without targeted immunotherapy drugs designed to interrupt the growth of cancer cells.
The CheckMate 7FL study aimed to investigate the benefit of adding the immunotherapy drug nivolumab – the drug used in the above-mentioned Hodgkin lymphoma clinical trial – to neoadjuvant therapy in patients with newly diagnosed early-stage high-risk ER+/HER2– breast cancer. Nivolumab blocks the programmed cell death protein 1 (PD-1) receptor on the immune system’s T cells. Normally, when PD-1 binds to partner proteins like programmed cell death ligand 1 (PD-L1), found on some cancer cells, it instructs T cells not to attack cancer cells. PD-1 inhibitors like nivolumab effectively prevent cancer cells from hiding from the immune system, allowing T cells to remain active and capable of attacking cancer cells.
In the present phase 3 trial, 510 patients were randomized to receive chemotherapy (anthracycline and taxane) with either intravenous nivolumab or placebo. The primary endpoint was pathological complete response (pCR) rates, which refers to the absence of detectable cancer cells in tissue samples after treatment and is used to assess how well a treatment has worked.
In patients treated with nivolumab plus chemotherapy, pCR rates were statistically significant, nearly double those who received placebo plus chemo: 24.5% versus 13.8%, respectively.
“These patients are considered to be likely cured because their tumor was removed and samples of breast and lymph node tissue collected at the same time also show no detectable cancer cells,” said Professor Sherene Loi, who led the trial and is the study’s lead and corresponding author. “The number of patients who achieved this pCR improved significantly as a result of nivolumab, an exciting result that points to a new treatment paradigm in this most common type of breast cancer.”
Interestingly, the pCR rate was even higher in a sub-group of patients with tumors that produced the PD-L1 biomarker: 44% in the nivolumab group compared to 20% who received the placebo. Longer follow-up will show whether these pCRs translate into better event-free survival (EFS) – how long a patient remains free of events like disease recurrence, progression, complications or death – for all breast cancer patients or just for patients with tumors that are PD-L1 positive.
The most common adverse events (AEs) were alopecia (hair loss), nausea, anemia, and fatigue, spread fairly evenly across the treatment and placebo groups. Serious AEs and treatment-related AEs, including those leading to discontinuation, were reported more with nivolumab than with placebo. Concerningly, there were five deaths in the nivolumab group, two related to drug toxicity.
Despite these safety concerns, the researchers were happy with the treatment effect they saw.
“Overall, these results represent a new milestone in the neoadjuvant treatment of ER+/HER2– BC [breast cancer], because there have been intensive but thus far unsuccessful efforts to improve pCR rates in this patient population,” they said.
The study was published in the journal Nature Medicine.
Source: Peter Mac
