A new analysis of people diagnosed with locally advanced or metastatic triple-negative breast cancer with specific biomarkers found that the immunotherapy Tecentriq (chemical name: atezolizumab) in combination with the chemotherapy Abraxane (chemical name: albumin-bound paclitaxel or nab-paclitaxel) only helps treat cancers that are positive for the biomarker PD-L1.
The research was presented on Dec. 5, 2018, at the San Antonio Breast Cancer Symposium. Read the abstract of “IMpassion130: Efficacy in immune biomarker subgroups from the global, randomized, double-blind, placebo-controlled, phase III study of atezolizumab + nab-paclitaxel in patients with treatment-naïve, locally advanced or metastatic triple-negative breast cancer.”
Locally advanced breast cancer is breast cancer that has spread to tissue near the breast, but not to parts of the body away from the breast. Metastatic breast cancer is cancer that has spread to parts of the body away from the breast, such as the bones or liver.
Triple-negative breast cancer is breast cancer that is:
Triple-negative breast cancers are usually more aggressive, harder to treat, and more likely to come back (recur) than cancers that are hormone-receptor-positive or HER2-positive. Triple-negative breast cancers don't usually respond to hormonal therapy medicines or the medicines that target the HER2 protein, such as Herceptin (chemical name: trastuzumab), Kadcyla (chemical name: T-DM1 or ado-trastuzumab emtansine), Nerlynx (chemical name: neratinib), Tykerb (chemical name: lapatinib), or Perjeta (chemical name: pertuzumab).
Right now, Tecentriq is approved by the U.S. Food and Drug Administration (FDA) to treat a type of bladder and urinary tract cancer called urothelial carcinoma and non-small cell lung cancer. Tecentriq currently is not approved to treat breast cancer.
Both Tecentriq and Abraxane are given intravenously as infusions, which means the medicines are delivered directly into your bloodstream through an IV or a port.
A biomarker is an aspect of something biological that can be measured or evaluated. In breast cancer, biomarkers can be used to figure out if a treatment could be effective against a cancer. For example, hormone receptor status is used to determine if hormonal therapy, such as tamoxifen or an aromatase inhibitor, will help treat a cancer. Hormonal therapy is effective against hormone-receptor-positive breast cancers and doesn’t work on hormone-receptor-negative cancers.
How do immunotherapy medicines work?
Immunotherapy medicines work by helping your immune system work harder or smarter to attack cancer cells. Immunotherapy medicines use substances — either made naturally by your body or man-made in a lab — to boost the immune system to:
- stop or slow cancer cell growth
- stop cancer cells from spreading to other parts of the body
- be better at killing cancer cells
There are several types of immunotherapy medicines. Tecentriq is an immune checkpoint inhibitor immunotherapy medicine.
To start an immune system response to a foreign invader, the immune system has to be able to tell the difference between cells or substances that are “self” (part of you) versus “non-self” (not part of you and possibly harmful). Your body’s cells have proteins on their surfaces or inside them that help the immune system recognize them as “self.”
Some of these proteins that help your immune system recognize “self” cells are called immune checkpoints. Cancer cells sometimes find ways to use these immune checkpoint proteins as a shield to avoid being identified and attacked by the immune system’s T cells.
Immune checkpoint inhibitors target these immune checkpoint proteins and help the immune system recognize and attack cancer cells. Immune checkpoint inhibitors essentially take the brakes off the immune system by blocking checkpoint inhibitor proteins on cancer cells or on the T cells that respond to them.
Tecentriq is a PD-L1 checkpoint inhibitor.
PD-1 is a checkpoint protein on T cells. PD-L1 is another checkpoint protein found on many healthy cells in the body. When PD-1 binds to PD-L1, it stops T cells from killing a cell. Some cancer cells have a lot of PD-L1 on their surface, which stops T cells from killing these cancer cells. An immune checkpoint inhibitor medicine such as Tecentriq that stops PD-1 from binding to PD-L1 allows T cells to attack the cancer cells.
The IMpassion130 study
The IMpassion130 study included 902 people — 898 women and four men — who had been diagnosed with locally advanced or metastatic triple-negative breast cancer. None of the people had been treated for advanced-stage disease yet.
The characteristics of the people in the study:
- Ages ranged from 20 to 86.
- About 67% were white, about 17% were Asian, about 6% were black, and about 4% were Native American.
- About 90% had been diagnosed with metastatic disease.
The researchers randomly assigned the people to receive one of two treatments:
- 451 people were treated with Tecentriq plus Abraxane.
- 451 people were treated with placebo plus Abraxane.
The people continued treatment until the cancer grew or unacceptable side effects developed.
In October 2018, IMpassion130 results were presented showing that Tecentriq plus Abraxane offered better progression-free survival and overall survival compared to Abraxane alone for the people in the study.
Because Tecentriq is a PD-L1 checkpoint inhibitor, the researchers specifically looked to see how well the medicine worked in the 369 people in the study diagnosed with breast cancer that was PD-L1-positive:
- 185 of these people were treated with Tecentriq plus Abraxane.
- 184 of these people were treated with Abraxane alone.
While progression-free survival — the time the people lived without the cancer growing — was similar to the overall survival results, overall survival was a bit better for people diagnosed with PD-L1-positive disease treated with Tecentriq plus Abraxane.
Are other biomarkers linked to Tecentriq’s effectiveness?
The researchers also wanted to know if there were other biomarkers in the breast cancers that could help figure out whether Tecentriq would be effective. These were the results presented at the 2018 San Antonio Breast Cancer Symposium.
The researchers looked at three other biomarkers:
- CD8 T cells: CD8 T cells are immune system cells that help the body attack foreign cells. The researchers measured the number of CD8 T cells that were inside the cancer tumor.
- Tumor-infiltrating lymphocytes (TILs): TILs are another type of immune system cell that have left the bloodstream and moved into a cancer tumor. Because these immune system cells are already in the cancer tumor, researchers think that a cancer with high levels of TILs may be more responsive to immunotherapy medicines.
- BRCA1 and BRCA2 mutation status: The researchers wanted to know if being BRCA1- or BRCA2-positive would affect how the cancer responded to Tecentriq.
Overall, PD-L1 was still the best indicator of whether Tecentriq could help treat breast cancer.
“The bottom line is that the breast cancers needed to be PD-L1-positive for atezolizumab to be effective,” said Leisha Emens, M.D., Ph.D., professor of medicine at the Hillman Cancer Center at the University of Pittsburgh Medical Center and co-leader of the Immunology and Immunotherapy Program and director of translational immunotherapy for the Women’s Cancer Research Center, who presented the research. “It was encouraging to see that cancers with even low levels of PD-L1 responded to Tecentriq,” she added. “Our analyses showed PD-L1 is the most robust predictive biomarker for selecting untreated metastatic triple-negative breast cancer patients who would benefit from the combination of atezolizumab and nab-paclitaxel.”
What about side effects?
As with most cancer medicines, Tecentriq and Abraxane may cause side effects, some of them severe.
In the IMpassion130 study:
- 99.3% of people treated with Tecentriq and Abraxane had side effects
- 97.9% of the people treated with Abraxane had side effects
The most common side effects in both treatment groups were:
- hair loss: 56.4% in the Tecentriq-Abraxane group and 57.5% in the Abraxane-alone group
- nausea: 46% in the Tecentriq-Abraxane group and 38.1% in the Abraxane-alone group
- cough: 24.8% in the Tecentriq-Abraxane group and 18.9% in the Abraxane-alone group
- peripheral neuropathy: 21.7% in the Tecentriq-Abraxane group and 22.1% in the Abraxane-alone group
- neutropenia (low white blood cell counts): 20.8% in the Tecentriq-Abraxane group and 15.3% in the Abraxane-alone group
- fever: 18.8% in the Tecentriq-Abraxane group and 10.7% in the Abraxane-alone group
- hypothyroidism (underactive thyroid): 13.7% in the Tecentriq-Abraxane group and 3.4% in the Abraxane-alone group
Severe side effects happened in:
- 48.7% of people treated with Tecentriq and Abraxane
- 42.2% of people treated with Abraxane alone
The most common severe side effects were low white blood cell counts, peripheral neuropathy, fatigue, and anemia. Rates of severe peripheral neuropathy were about twice as high in the Tecentriq-Abraxane group (5.5%) compared to the Abraxane-alone group (2.7%).
What do these results mean for you?
While the results of the IMpassion130 study are very exciting and promising, it’s important to know that the follow-up for the study was only about a year. Longer follow-up time will offer more information on how long the cancers respond to Tecentriq, as well as whether it’s possible for people to ever stop treatment with Tecentriq.
It’s expected that Roche, the company that makes Tecentriq, will ask the FDA to approve a breast cancer indication for the medicine.
It’s also important to know that Tecentriq costs about $12,500 per month. Because Tecentriq is not yet FDA approved to treat breast cancer, it’s unclear how many insurance providers will cover the cost for breast cancer treatment with Tecentriq.
If you’ve been diagnosed with locally advanced or metastatic triple-negative breast cancer and are deciding on treatments for the advanced-stage disease, you may want to talk to your doctor about this study. You may want to ask if it’s possible to do PD-L1 testing on the cancer to see if you might benefit from a PD-L1 checkpoint inhibitor such as Tecentriq. You also may want to ask about other clinical trials looking at Tecentriq and other immune checkpoint inhibitors and whether any of them might be a good fit for your unique situation.
For more information on immunotherapy medicines, how they work, and their possible side effects, visit the Breastcancer.org Immunotherapy section.
To discuss immunotherapy options with others, join the Breastcancer.org Discussion Board forum Immunotherapy – Before, During, and After.
Editor’s Note: On March 8, 2019, the FDA approved Tecentriq in combination with Abraxane as a first treatment for unresectable locally advanced or metastatic triple-negative, PD-L1-positive breast cancer.
Written by: Jamie DePolo, senior editor
Reviewed by: Brian Wojciechowski, M.D., medical adviser