Some women with the most-difficult-to-treat form of advanced breast cancer who have positively responded to atezolizumab (Tecentriq) are reporting panic and anxiety because oncologists have suddenly discontinued their prescription.
The discontinuance appears to be in reaction to an announcement by the manufacturer (Genentech) in late August that it is voluntarily withdrawing its application for accelerated approval of the drug for use in metastatic triple-negative breast cancer (mTNBC).
However, experts stress that discontinuing atezolizumab is not advised if a patient is responding to or is stable on the immune checkpoint inhibitor.
“I think the Genentech announcement has been misinterpreted,” Maryam Lustberg, MD, MPH, of Yale Cancer Center, New Haven, Connecticut, told Medscape Medical News. “The consensus opinion from all academic breast oncologists is that people should not be switching off atezolizumab if they are responding. They should not be changing their immunotherapy.”
Lustberg said the announcement had two major points: “don’t start a new patient on atezolizumab,” and the company is “committed” to supplying the drug to patients whose conditions are stable or responding.
Nevertheless, some patients with mTNBC were recently in a state of escalating emotional upset, said one patient advocate last week.
“The level of panic among those currently on & responding well to atezo is growing quickly,” tweeted Janice Cowden, a former nurse living with mTNBC in Bradenton, Florida.
Cowden explained that “at least 10-20 patients” were “pulled [off the drug by their oncologist] this past week who have been stable/no evidence of disease/no evidence of disease activity on Tecentriq.”
She estimated that as many as 50 patients in the 2200-member Triple Negative BC Stage 4 Facebook group who have been responding to the drug were abruptly de-prescribed atezolizumab since the August 27 announcement from Genentech.
Many women learned of the change via patient portals or text messaging, not directly from their physicians, Cowden told Medscape Medical News.
Some of the women had been taking atezolizumab for 2 to 3 years, including those with no evidence of disease, she said. “Finding out that their oncologist was discontinuing a treatment that was working for them has been driving so much anxiety and stress,” Cowden emphasized.
Most market withdrawals of drugs are related to safety, but that is not the case with atezolizumab, said Sara Horton, MD, of Howard University, in Washington, DC. She was speaking this week at a Facebook webinar on atezolizumab and mTNBC that was sponsored by the TNBC Foundation and the Young Survivors Coalition.
In the case of atezolizumab, it was a question about efficacy that prompted the withdrawal. After the indication was granted an accelerated approval on the basis of response data, a confirmatory trial set out to show clinical benefit. However, the confirmatory phase 3 IMpassion131 trial did not do so: it found that atezolizumab plus paclitaxel did not significantly reduce the risk for cancer progression and death in comparison with paclitaxel plus placebo among patients with TNBC with tumors that were positive for programmed cell death protein–1 (PD-L1), as reported by Medscape Medical News.
These results were discussed by the US Food and Drug Administration (FDA) on the first day of a historic 3-day meeting on accelearted approvals in April 2021. Despite the failure of confirmation of clinical benefit, the advisory panel voted 7-2 in favor of keeping the approval in place for atezolizumab in TNBC. At the same time, it urged Genentech to carry out more studies to show that the drug works in this patient population.
The company apparently decided not to do that and instead voluntarily withdrew the application for the indication some 4 months later.
During the recent TNBC Foundation webinar, Genentech official Lauren Davis, MBA, said that the company sent letters about this decision to atezolizumab-prescribing physicians and included another letter that was to be shared with patients. Davis had not responded to Medscape’s request to review the communications at the time this article was published.
At the webinar, Davis did clarify that current atezolizumab patients (who are responding to the drug), who have commercial insurance, and who benefit from Genentech’s copay program will continue to receive the benefit until June 2022.
In its August announcement, Genentech said it decided to withdraw the atezolizumab approval on the basis of the FDA’s assessment of the “current mTNBC treatment landscape and in accordance with the requirements of the accelerated approval program.”
That landscape presumably includes pembrolizumab (Keytruda), which received a full approval for a TNBC indication similar to that of atezolizumab 2 months ago. That full approval was based on findings from the randomized, phase 3 KEYNOTE-522 trial, which showed significantly prolonged event-free survival with the pembrolizumab regimen in comparison with neoadjuvant chemotherapy alone for previously untreated stage II or III TNBC. Details of these clinical data will be presented at the upcoming annual meeting of the European Society of Medical Oncology.
Switching the Immunotherapy?
Some US oncologists have been telling patients with mTNBC that the atezolizumab withdrawal is “not an issue” because the new full approval of pembrolizumab in this setting will allow prescriptions to be switched, said patient advocate Cowden.
However, experts have said that no patient who is responding to or whose condition is stable with atezolizumab should switch immunotherapies. “This is a very aggressive disease,” reminded Lustberg.
Switching the immunotherapies is complicated by the difference in the respective drugs’ companion biomarker assays used to establish the presence of PD-L1.
Lustberg explained that patients who are not responding to atezolizumab and who now want to try pembrolizumab will have to be assessed with the CTS assay.
“About 22% of the patients who are positive for the atezolizumab biomarker assay SP-142 are not going to be positive for the CTS,” she said.
In other words, about 1 in 4 patients with mTNBC who are taking atezolizumab will not qualify for treatment with pembrolizumab.
Rebecca Shatsky, MD, of the University of California, San Diego, echoed those comments in an email to Medscape Medical News ― and emphatically discouraged switching off atezolizumab (and going on pembrolizumab) if a patient is having success (ie, stable disease or positive response).
“The two groups don’t always overlap, so it isn’t an easy switch. That’s why if they are already responding, I would NOT have them stop the drug,” she said.
Not every mTNBC patient receiving ― and responding to ― atezolizumab has had the unfortunate experience of having their prescription canceled.
Johanna Rauhala, of San Francisco, California, who is a former middle-school teacher and who writes the blog pinkstinks, has been taking atezolizumab for 2 years. She has had a partial response and now, after taking the immunotherapy in combination with chemotherapy (gemcitabine and carboplatin), has stable disease. Currently, she is taking single-agent atezolizumab..
Rauhala has been living with mTNBC for 5 years. She told Medscape Medical News that she was “very surprised and concerned” to learn about Genentech’s withdrawal of its accelerated approval. She has a treatment appointment this week. “I’m probably going to ask the oncology nurse first [about the atezolizumab withdrawal] ― because they are the front line, and I will then follow-up with my doctor. But I can’t imagine that they will take away something that is working.”
Shatsky, Horton, and Lunsberg report no relevant financial disclosures.
Nick Mulcahy is an award-winning senior journalist for Medscape. He previously freelanced for HealthDay and MedPageToday and had bylines in WashingtonPost.com, MSNBC, and Yahoo. Email: [email protected] and on Twitter: @MulcahyNick.