By Karuna Jaggar, Executive Director
The U.S. Food and Drug Administration (FDA)’s recent approval of the first immunotherapy drug for breast cancer has been hailed as “exciting” and “revolutionary” by some in the medical field.
At Breast Cancer Action, we’re less impressed.
Atezolizumab (brand name Tecentriq) was approved for a subset of women with metastatic triple-negative breast cancer with PD-L1-positive tumors. These are aggressive and hard to treat cancers, for which we urgently need effective treatments.
Unfortunately, while initial data shows potential promise, the approval is premature as there is not yet clear evidence that atezolizumab helps these women live longer or improves their quality of life.
The experimental drug also ranks among the most expensive breast cancer treatments, with a list price of $13,400 a month.
The FDA’s accelerated approval of atezolizumab was based on the 902-patient Phase 3 IMpassion130 trial, which showed that the tumors of patients who took the drug in combination with chemotherapy grew more slowly—what’s known as longer progression-free survival—than patients who had chemo alone.
The median progression-free survival among the entire study population was 7.2 months with the combination and 5.5 months with chemotherapy alone, at just over a year of follow up. In the PD-L1–positive group, which was around 40 percent of the enrolled patients (369 of 902), the median progression-free survival was 7.5 months with the combination and 5.0 months with chemotherapy alone.
An interim assessment found a trend toward improved overall survival, but relied on “some statistical shenanigans with addition of a second trial endpoint and enrollment of more patients,” noted Elaine Schattner. According to a subset analysis, median overall survival for patients with PD-L1–positive tumors was 25.0 months with the combination treatment, compared to 15.5 months with standard chemotherapy alone.
While researchers described the treatment as “well tolerated,” women who took atezolizumab did experience more serious side effects, and three deaths were attributed to the immunotherapy treatment.
At Breast Cancer Action we’ve long argued that drugs should receive FDA approval only if they extend overall survival, improve quality of life, or cost less than therapies already available. Because people with metastatic breast cancer want to live longer. Or if the treatment won’t help extend life, it should at least be less toxic than existing treatments, with reduced side effects. And if a new drug doesn’t do either of those things, the only other way it’s a benefit to patients is if it costs less than existing therapies.
The length of time with no tumor growth while on a specific treatment is called Progression Free Survival (PFS). But surrogate endpoints, such as PFS aren’t always associated with improved overall survival or improved quality of life. While these endpoints may be useful, indicating an experimental drug appears to have some positive effect on the tumor, it’s not enough to show true clinical benefit.
We have opposed the FDA’s approval of other drugs that have not met this standard, including:
- Nerlynx (neratinib), a so-called “extended therapy” for early-stage HER2-positive breast cancer
- Ibrance (palbociclib), to treat metastatic hormone positive, HER2-negative breast cancers in post-menopausal women
- Lyparza (olaparib), to treat HER2-negative metastatic breast cancer in patients with a BRCA gene mutation who have previously been treated with chemotherapy.
Roche, the company that makes atezolizumab, has pointed out that the FDA could yank the drug’s approval for triple-negative breast cancer if further studies don’t prove there’s a meaningful benefit for patients. But it took more than three years for the toxic drug Avastin (bevacizumab), which was similarly fast-tracked based on progression-free survival, to be pulled after better data failed to show it helped women with breast cancer. In the meantime, Roche stands to make millions without having proven that the treatment really helps patients.
Women with triple-negative breast cancer deserve and urgently need drugs that work. But because these cancers don’t express estrogen receptor, progesterone receptor or HER2 genes, there are currently fewer treatment options for these aggressive cancers. Triple-negative breast cancer accounts for a higher number of breast cancer deaths and is more likely to affect African-American and young women (only about 6.5 percent of women in the phase 3 trial were African-American).
But lowering the bar in order to approve a drug doesn’t save lives if that drug doesn’t work. Setting the approval bar too low for breast cancer drugs also diverts resources from efforts to spearhead real innovation. The reality is that as of now, atezolizumab can’t be counted as an exciting advance.
Once again, we’re calling on the FDA to tighten its drug approval standards in order to incentivize real progress in breast cancer treatment. With this latest approval of yet another expensive drug without proof of any benefit, the FDA is allowing a drug company to profit from an unproven drug, subjecting women to physical and financial toxicity without demonstrated benefit.