Roche’s Multifaceted Drug, Tecentriq Registers Mixed Results in Breast Cancer Patients

By T. Chakraborty, Ph.D.

The most common type of cancer amongst women is breast cancer, which affects upwards of two million each year. Triple-negative breast cancer (TNBC) comprises about 15% of all breast cancer cases and is significantly predominant in women under 50. TNBC is defined as the lack of estrogen, progesterone receptors, and HER2 protein (the cells test negative on all three tests, hence called “triple-negative”). Earlier this week, Roche announced that it had presented the latest data from three Phase III trials (IMpassion031, IMpassion130, IMpassion131) at the European Society for Medical Oncology (ESMO) Virtual Congress 2020, which evaluated Tecentriq (atezolizumab) in treating TNBC [1].

Tecentriq

Immune cells of our body play an important role in cellular proliferation. Immune checkpoint proteins keep the immune cells from persistent activation, thereby striking a balance between inflammatory and anti-inflammatory states. Cancer cells take advantage of these proteins, thereby evading the host immune system.

Since the discovery of these checkpoint proteins in cancer, immunotherapy targeting these proteins have gained momentum. One such immune regulatory protein is programmed death receptor 1 or PD-1. PD-1 is generally present on the surface of immune cells, inhibiting the normal functions of the cell. Tecentriq is a monoclonal antibody targeting the ligand of PD-1. This immunotherapy has been widely successful in various types of cancers and is approved in more than 70 countries.

IMpassion Clinical Trials

IMpassion031 study

The IMpassion031 clinical trial is a Phase III randomized trial in which 333 patients with early triple-negative breast cancer patients were enrolled. The study aimed to test the efficacy and safety of Tecentriq in combination with chemotherapy agents. The primary endpoint of the study, pathological complete response, was significantly enhanced in the treatment group (57.6%) compared to patients in the placebo group (41.1%). The safety profile of the drug was consistent with the chemotherapy group alone. This study is the first to demonstrate the efficacy of Tecentriq in the treatment of early triple-negative breast cancer. Unfortunately, this positive result was not recapitulated in other clinical trials [1].

IMpassion130 study

The IMpassion130 study is a Phase III clinical trial that recruited 902 patients with advanced metastatic breast cancer. This study evaluated the efficacy and safety of Tecentriq along with chemotherapy agent nab-paclitaxel. The primary endpoints of the study, progression-free survival, and overall survival, were not significantly altered by treatment with the drug compared to the control group. Though Tecentriq treated patients had an overall increase in survival by 7.5 months, and this increase was clinically relevant, it never reached statistical significance.

IMpassion131 study

The IMpassion131 study is a Phase III clinical trial, in which 651 people who were previously untreated and had locally advanced breast cancer were enrolled. The patients were administered Tecentriq in combination with paclitaxel. The primary endpoint, progression-free survival, was not significantly altered in patients treated with Tecentriq than controls. Further, overall survival showed a negative trend.

Dr. Levi Garraway, Roche’s Chief Medical Officer and Head of Global Product Development conceded, “While we have made great progress in the treatment of many forms of breast cancer, TNBC remains an aggressive and difficult-to-treat disease. We are proud of our work to address challenges and advance scientific understanding of cancer immunotherapy in the context of distinct chemotherapy regimens and various TNBC treatment settings. Although the IMpassion131 study did not reach its endpoint, we are pleased to bring new treatment options for some TNBC patients and remain committed to improving the lives of all women with early and advanced stages of this disease.” [1]

These mixed results for Tecentriq may further enhance the revenue of its competitor, Merck’s blockbuster drug Keytruda, which has gained prominence in different cancer types since its first approval in 2014. Merck recently inked a deal with Seattle Genetics for their experimental anti-LIV-1 antibody-drug conjugate named ladiratuzumab vedotin, which will be combined with Keytruda in metastatic TNBC trials [2].

Editor: Rajaneesh K. Gopinath, Ph.D.

Related Article: Trodelvy Gives New Hope to Patients with Relapsing Breast Cancer

References

1. https://www.roche.com/media/releases/med-cor-2020-09-19.htm
2. https://www.geneonline.com/2020/09/16/merck-bets-big-on-seattle-genetics-for-two-oncology-drugs/

Author

Tulip Chakraborty