Tecentriq-Abraxane Combo Prolonging Survival in TNBC Patients, Phase 3 Trial Data Show

Tecentriq in combination with Abraxane, a  chemotherapy, continues to prolong overall survival in adults with triple-negative breast cancer (TNBC) who test positive for the PD-L1 factor, a new interim analysis from a Phase 3 trial shows.

These findings were detailed in an oral session, “IMpassion130: updated overall survival (OS) from a global, randomized, double-blind, placebo-controlled, Phase III study of atezolizumab (atezo) nab-paclitaxel (nP) in previously untreated locally advanced or metastatic triple-negative breast cancer (mTNBC),” presented at the recent 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.

Tecentriq (atezolizumab) is an immune checkpoint inhibitor, (developed by Genentech, a Roche subsidiary), approved to treat certain types of cancer, including bladder and non-small cell lung cancer.

An antibody, it is designed to bind to PD-L1, or programmed death-ligand 1, a substance produced by cancer cells. This effectively prevents PD-L1 from binding to its receptor, the PD-1 receptor, which can be found on the surface of immune cells. By doing so, Tecentriq blocks the signaling cascade that allows cancer cells to evade being targeted and killed by immune cells.

Abraxane (nab-paclitaxel) is a standard chemotherapy agent for patients with advanced forms of breast cancer; it is also approved for those with metastatic non-small cell lung cancer and pancreatic cancer.

The effectiveness of Tecentriq plus Abraxane as a first-line treatment for adults with advanced forms of TNBC is currently being tested in the multi-center, randomized, double-blind, IMpassion130 Phase 3 trial (NCT02425891).

The trial has enrolled 902 TNBC patients from 41 countries who had no previous treatment for their locally advanced or metastatic breast cancer. Participants were randomly divided into two groups of 451 each, and assigned to either intravenous infusions of Tecentriq or a placebo every two weeks, together with weekly Abraxane sessions for the first three weeks, over a treatment cycle of 28 days (about one month).

Data from a first interim analysis of IMpassion130, presented at the ESMO Congress last year, showed the Tecentriq-Abraxane combo extended the median time patients lived without their disease worsening (progression-free survival) from 5.5 months to 7.2 months.

The combination of Tecentriq and Abraxane also expanded patients’ median overall survival to 21.3 months, compared to 17.6 months among those given a placebo plus Abraxane. However, this difference was not sufficient to be considered statistically significant.

But the combo treatment significantly improved — to 25.0 months — the median overall survival in patients with PD-L1-positive tumors, compared to 15.5 months observed in patients treated with Abraxane alone (the control group).

Roche announced at ASCO these new findings from the study’s second interim analysis, whose data cut-off  date was Jan. 2:

• Tecentriq-Abraxane in combination extended median overall survival of TNBC patients to 21 months, compared to 18.7 months in the control group; however, these differences remained non-significant;
• Tecentriq-Abraxane led to statistically significant improvement in the median overall survival of patients with PD-L1-positive tumors, compared to similar people given placebo plus Abraxane (25.0 versus 18.0 months, respectively);
• More than half (51%) of the patients with metastatic TNBC and PD-L1-positive tumors were still alive after two years of treatment with the combo therapy, compared to 37% of people with similar cancers given Abraxane alone.

Additional analyses of patient-reported outcomes found the combo therapy was well-tolerated, similar to Abraxane when administered alone. Moreover, the combo therapy did not negatively affect patients’ quality of life or daily activities, and or show evidence of additional toxicity in side effects compared to Abraxane alone.

The combo regimen’s safety profile appears to be consistent with previous data, an expanded safety analysis showed. No new safety concerns have been reported.

“We are continuing our transformative work in breast cancer, presenting updated interim overall survival results from our Phase 3 Tecentriq combination, the first positive immunotherapy study in PD-L1-positive metastatic triple-negative breast cancer, a disease with high unmet need,” Sandra Horning, MD, chief medical officer and head of global product development at Roche, said in a press release.

Patients participating in IMpassion130 will continue to be followed. The Phase 3 study is due to end in April 2020.