Immunotherapy Shown for the First Time to Prolong Survival in Breast Cancer

In Munich, Germany, the ESMO 2018 Congressreported results simultaneously published in NEJMfrom IMpassion130 , a study called this, clinical trialwhose results showed that in metastatic (stage 4) triple-negative breast cancer some patients benefited from an immunotherapy drug, atezolizumab, which increased survival.

- Related topic: What Is Triple-Negative Breast Cancer? How Is It Diagnosed and Treated? (Detailed)

The study's lead author, Professor Peter Schmid, said the results "will change the way triple-negative breast cancer is treated" and continued: "Nab-paclitaxel in combination with atezolizumab is the first immunotherapy approach shown to improve survival in metastatic triple-negative breast cancer."

- Related Topic: Immunotherapy and Cancer Vaccines 

Atezolizumab is directed at a receptor on the surface of cancer cells, PD-L1 and is a monoclonal antibody immunotherapy drug. Most patients whose survival increased in this study had PD-L1-positive breast tumors.

PD-L1 is an immune system checkpoint, and blocking its function may activate the immune system against cancer cells. One way cancer cells evade the immune system is by having much more of the PD-L1 receptor on their surface than normal, a condition called PD-L1 positivity.

Triple-negative breast cancer is an aggressive type of breast cancer because its cells divide rapidly and tend to metastasize more. Triple-negative breast cancer lacks receptors for estrogen or the HER2 protein, meaning it cannot be treated with hormone therapy or HER2-targeted drugs . The main drug treatment for this type of breast cancer is chemotherapy, and patients tend to develop chemotherapy resistance within months. This type of breast cancer is relatively rare and usually affects young women. When the disease becomes metastatic, median survival is approximately 12 to 15 months.

Study details

The phase-3 IMpassion 130 clinical trial enrolled 902 triple-negative breast cancer patients who had not previously received treatment for metastatic disease. Patients received standard chemotherapy (nab-paclitaxel) plus atezolizumab or standard chemotherapy plus placebo and were randomized to two arms.

Two main endpoints were determined for the study:

1. how much the immunotherapy and chemotherapy combination slowed cancer (progression-free survival) in both PD-L1-positive and negative patients, and
2. how much it prolonged life (overall survival).

Median follow-up in the study was 12.9 months.

Study results

• Combination treatment with immunotherapy reduced the risk of disease worsening or death in all patients by % 20, and in the PD-L1-positive subgroup by % 38.
• For all patients, median progression-free survival (the time cancer is kept under control with treatment) was 7.2 months in the combination group) versus 5.5 months with chemotherapy alone. In the PD-L1-positive group, median progression-free survival was 7,5 months with the combination and 5 months with chemotherapy alone.
• More than half of the patients were alive at the time of analysis, so only a preliminary/interim assessment of overall survival could be made. In patients with PD-L1-positive tumors, median overall survival was 15.5 months with standard chemotherapy alone, while in the immunotherapy combination arm it was 25 months .
• The proportion of patients responding to treatment was % 56 in the combination arm versus % 46 in those receiving chemotherapy alone. In patients with PD-L1-positive tumors, the difference in response rates was greater (% 59 versus % 43).

Professor Schmid said the combination treatment was well tolerated. Most side effectswere due to chemotherapy, and side effects occurred at similar rates in both treatment groups, although there was a small increase in nausea and cough in the combination group. Side effects related to immunotherapy were rare, and the most common immunotherapy-related side effect was hypothyroidism (combination treatment group % 17.3 versus % 4.3 in those receiving chemotherapy alone).

- Related topic: What Are the Side Effects of Immunotherapy Drugs, and How Are They Treated?

Conclusion

These results are very noteworthy because, in stage 4 triple-negative breast cancer, adding immunotherapy to standard chemotherapy extended overall survival in patients with PD-L1-positive tumors by nearly 10 months (to 25 months).

Previously, another study presented at ASCO 2017, neoadjuvant (preoperative tumor-shrinking) chemotherapy+immunotherapy (pembrolizumab) had been shown to increase the pathological complete response rate. However, this study is the first randomized phase-3 clinical trial providing evidence that adding immunotherapy to standard chemotherapy improves survival in metastatic triple-negative breast cancer. The survival difference is particularly pronounced in patients with PD-L1-positive tumors, and approximately %40 of triple-negative breast tumors were PD-L1-positive. In conclusion, the IMpassion 130 data will probably change our treatment plan for patients with metastatic triple-negative breast cancer.