Roche’s Tecentriq made history last year as the first immuno-oncology agent to win an FDA nod in triple-negative breast cancer. But disappointing data unveiled toward the end of 2019 cast doubt on its potential for use before patients' tumors were removed.
Now, that hope has been rekindled.
Significantly fewer TNBC patients who got a combination of Tecentriq and chemotherapy ahead of surgery had signs of cancer in tissues removed by their surgeons—known as pathologic complete response (pCR)—compared with those on chemo alone, Roche said Wednesday.
The result was achieved in patients with early invasive TNBC regardless of PD-L1 expression, whereas Tecentriq’s current TNBC approval is for PD-L1-positive, metastatic disease.
Detailed data from the phase 3 IMpassion031 trial will be presented at an upcoming medical meeting. But the headline win comes in stark contrast to a defeat in the same setting for an investigator-sponsored trial unveiled at the San Antonio Breast Cancer Symposium in December.
At that time, researchers in Italy said adding Tecentriq to chemo in patients before surgery failed to improve pCR over chemo alone. That measure of response is a common alternative gauge of pre-surgery treatment in breast cancer, and it comes earlier than data on how long a patient remains cancer-free, otherwise known as event-free survival.
Tecentriq’s defeat in that NeoTRIPaPDL1 trial came as Merck & Co.’s Keytruda touted a win in the same setting. In the phase 3 Keynote-522 trial, a Keytruda-chemo combo in pre-surgery patients showed a pCR in 64.8% of them, while 51.2% on chemo alone could say that.
Then why did IMpassion031 succeed when NeoTRIPaPDL1 failed in basically the same patient population? There are many differences between the trials.
For one thing, the backbone chemotherapies are different. In the Roche trial, Tecentriq is paired up with Bristol Myers Squibb’s Abraxane—the same regimen used for metastatic TNBC—and then later with doxorubicin and cyclophosphamide. As for the Italian study, the PD-L1 drug is given alongside a combination of carboplatin and Abraxane. The treatment cycles and the Tecentriq dosing frequency also differed.
Now, Roche is hoping its own top-line readout could pave the way for regulatory approvals for Tecentriq in the neoadjuvant setting, just as Keytruda is chasing it in metastatic TNBC.
Just last month, Merck revealed that Keytruda, used alongside chemo, cut the risk of disease progression or death by 35% compared with solo chemo in previously untreated, metastatic TNBC patients with certain levels of PD-L1. In its separate study, the Tecentriq-Abraxane pairing pared down that risk by about 40% in PD-L1-positive TNBC patients.