Combining Tecentriq (atezolizumab) with the chemotherapy Abraxane (nab-paclitaxel) extends overall survival, and survival without cancer progression, in patients with triple negative breast cancer (TNBC) whose cancer is locally advanced or has spread to distant regions in the body, a Phase 3 clinical trial shows.
Combo therapy prolonged patients’ overall survival particularly in those with PD-L1 positive tumors, who lived nearly 10 months longer. Also, the treatment was considered well-tolerated, causing no unexpected adverse side effects.
The interim results of the study were presented at the European Society for Medical Oncology (ESMO) 2018 Congress held Oct. 19-23 in Munich, Germany.
They also were published in the report, “Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer,” in the journal New England Journal of Medicine.
The trial is evaluating the combination of Tecentriq (developed by Genentech-Roche) with the chemotherapy Abraxane as a first-line treatment for metastatic TNBC and locally advanced cancer in patients who cannot undergo surgery.
Tecentriq is a blocking antibody that selectively targets PD-L1, belonging to a type of anti-cancer drugs called checkpoint inhibitors. It is approved for some patients with metastatic urothelial carcinoma or non-small cell lung cancer.
Abraxane is a standard chemotherapy for patients with metastatic breast cancer, also approved for metastatic non-small cell lung cancer and pancreatic cancer.
The combination between both agents is being studied in the IMpassion130 trial (NCT02425891), an international and multicenter, randomized, double-blind Phase 3 study. A total of 902 patients have been enrolled from 41 countries in Europe, the United States and Canada, Asia, Latin America, and Australia.
Patients were divided in two groups of 451 and were assigned randomly to receive either Tecentriq or a placebo, given intravenously every two weeks, along with weekly chemotherapy with Abraxane for the first three weeks, over a 28-day cycle.
Treatment was continued until patients had signs of cancer progression or experienced unacceptable toxicity.
For patients receiving Tecentriq-Abraxane, median duration of treatment was 24.1 weeks; in the control group (Abraxane plus placebo), median duration was 21.8 weeks. Median follow-up was 12.9 months.
Nearly half of the patients (40.9%) had PD-L1–positive tumors, detected as the presence of tumor-infiltrating immune cells expressing PD-L1 on their surface.
In the entire study population, Tecentriq-Abraxane combo extended the median time to disease progression or death (progression-free survival) to 7.2 months compared with 5.5 months for patients in the Abraxane plus placebo.
The combo also prolonged median overall survival to 21.3 months, compared with the control treatment, which led to a median survival of 17.6 months. However, this difference was not statistically significant.
Of note, patients with PD-L1–positive tumors seem to have benefited the most from the combo treatment, with a median overall survival of 25.0 months, compared with 15.5 months in the control group.
However, owing to the fact that only an interim analysis was possible at the time of data cut-off, no statistical analysis could be done.
Combo treatment also led to a numerically higher objective response rate (percentage of patients with tumor shrinkage) in patients receiving the combo therapy versus the control group (56.0% vs. 45.9%).
Agreeing with survival results, in the PD-L1–positive group, the effect was larger, leading to response rates of 58.9% versus 42.6%.
In terms of safety, no unexpected adverse effects were reported and the treatment was well-tolerated, according to researchers. Adverse side effect were consistent with the toxic effects of Tecentriq and Abraxane known from prior studies.
“Atezolizumab in combination with nab-paclitaxel is the first targeted treatment to improve survival in metastatic triple negative breast cancer,” Peter Schmid, MD, PhD, first author of the study, said in an ESMO press release.
“It is also the first immune therapy to improve outcome in this cancer. Most of the survival benefit was in patients with PD-L1 positive tumours,” added Schmid, who is also lead of the Centre for Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University of London, U.K.
Despite the relatively small benefit seen in progression-free survival, “the gain in overall survival in the PD-L1 positive subgroup was impressive with a ten-month benefit. Around 40% of the tumours were PD-L1 positive,” said Marleen Kok, MD, oncologist at The Netherlands Cancer Institute. “The IMpassion 130 data will probably change the treatment landscape for our metastatic triple negative breast cancer patients.”
Given the greater effect over PD-L1 positive, researchers also stress in the study it is important to consider patients’ PD-L1 expression status “to inform treatment choices for patients with metastatic triple-negative breast cancer.”