By Karuna Jaggar, Former Executive Director and SABCS Guest Writer
Atezolizumab (brand name Tencentriq) was the first immunotherapy approved for breast cancer, just over a year and a half ago, as noted in my first immunotherapy blog post, for metastatic triple negative breast cancer. Now researchers are exploring the use of this immunotherapy in early stage breast cancer, including looking at side effects to balance harms and potential benefits.
Before turning to the new data presented at the San Antonio Breast Cancer Symposium (SABCS), it’s helpful to understand the current data regarding atezolizumab. The FDA’s 2019 accelerated approval was based in a surrogate endpoint, and mixed overall survival data was presented in September of this year at the ESMO Virtual Congress 2020. Final analysis of the phase 3 IMpassion 130 trial showed an improvement of 7.5 months in overall survival (25.4 versus 17.9 months) for patients with metastatic, PD-L1 positive, triple negative breast cancer who were treated with atezolizumab plus nab-paclitaxel (also known as protein-bound paclitaxel). Additionally, the, 3-year survival rate for those in the in the PD-L1 positive population who received the atezolizumab and nab-paclitaxel combination was 36% compared to 22% for those who received chemo alone. However, there was no benefit for patients in the same group whose tumors were PD-L1 negative.
The researchers also found no benefit when atezolizumab was paired with a different chemotherapy, paclitaxel. Not only was there no survival benefit when paclitaxel was used instead of plus nab-paclitaxel in combination with atezolizumab, the interim analysis favored paclitaxel alone compared to those who also received the immunotherapy. In response to this new data, the FDA issued an alert warning providers when treating atezolizumab in clinical practice, not to replace nab-paclitaxel with paclitaxel.
Metastatic triple negative breast cancer remains hard to treat and even when drugs like atezolizumab “work,” they are hardly a cure. In an attempt to prevent metastasis in the first place, researchers often experiment with using drugs that are effective in treating advanced breast cancer to treat patients with early breast cancer. It is no surprise then that there is interest in including immunotherapies in treatment of early stage breast cancer in the hopes of avoiding metastasis in the first place.
The IMpassion 031 trial reported by Dr. Beth Mittendorf on Thursday morning (GS3-02) looked at the use of atezolizumab before surgery (neoadjuvant therapy) for patients with early stage triple negative breast cancer (TNBC). Because early stage breast cancer is largely asymptomatic, the first time most of these patients feel sick is when they are undergoing treatment. For this reason, the researchers focused on patient reported outcomes of adding immunotherapy to treatment for early stage breast cancer.
The researchers had previously reported improved pathologic complete response (pCR) for the combination of atezolizumab and chemotherapy in early stage TNBC, in the first analysis of checkpoint inhibitor therapy (a type of immunotherapy) in early stage breast cancer. As a reminder pCR refers to the disappearance of invasive cancer in the breast and lymph nodes in response to systemic therapy (like chemotherapy) before surgery. It’s used to evaluate the efficacy of treatment as well as to predict how well patients will do. However, overall survival data remains the only way to know if patients actually live longer as a result of treatment.
In the first analysis of patient reported outcomes for checkpoint inhibitor therapy for patients with early triple negative breast cancer, Dr. Mittendorf reported on quality of life during the 4-6 months people receive these therapies. At the beginning of the study, health related quality of life was high at baseline and declined when treatment began. The most common treatment-related symptoms were fatigue, nausea and vomiting, and diarrhea—all symptoms that are common with chemotherapy.
The researchers found that there were no major differences in quality of life or day to day functioning between those who received chemotherapy alone and those who received chemo plus the immunotherapy atezolizumab. Quality of life decreased for everyone being treated for early stage triple negative breast cancer, regardless of which treatment arm they were in. After treatment, quality of life rebounded for everyone, including for those who received immunotherapy in addition to their chemotherapy.
The data shows that adding the checkpoint inhibitor atezolizumab to chemotherapy before surgery for early triple-negative breast cancer does not worsen patient reported quality of life. However, the cost of treatment was not considered, and there is concern about the high cost of immunotherapies. It is estimated that atezolizumab adds approximately $120,000 to the cost of treatment. A paper published in ASCO Journal and funded by the National Cancer Institute (NCI) concluded: “Despite improved clinical outcomes, the addition of atezolizumab would not be considered cost effective in part due to the high costs of stable disease and disease progression among women with advanced TNBC. Novel therapeutics in this costly patient cohort will need to bend the cost curve of stable and progressive disease before becoming cost effective at thresholds acceptable by today’s standards.” Elsewhere, researchers in Singapore similarly concluded that “adding atezolizumab to nab-paclitaxel was unlikely to represent good value for money for the treatment of advanced PDL1-positive TNBC.”
Although prior studies show improved tumor response (pCR) for people with early stage triple negative breast cancer, it remains to be seen if this will translate to overall survival benefit. If so, it’s worth asking, given that the major toxicity comes from chemotherapy and not from adding atezolizumab, if immunotherapy alone (skipping chemotherapy) might prove equally effective, but less toxic.