Leisha A. Emens
Atezolizumab monotherapy appeared safe and provided durable clinical benefit among patients with metastatic triple-negative breast cancer, according to results of a multicenter phase 1 study.
Researchers observed the most significant survival benefit among women who received atezolizumab (Tecentriq, Genentech) as first-line therapy, and among those with higher levels of tumor-infiltrating immune cells and PD-L1-positive immune cells.
“Our study shows that atezolizumab monotherapy is well-tolerated in patients with metastatic triple-negative breast cancer, and it can provide durable clinical benefit in patients with PD-L1-positive disease as well as when given in the first-line for advanced-stage disease,” Leisha A. Emens, MD, PhD, professor of medicine at the UPMC Hillman Cancer Center/Magee Women’s Hospital, and director of translational immunotherapy for the Women’s Cancer Research Center in Pittsburgh, told HemOnc Today.
The multicohort, open-label, phase 1 study included 116 women (median age, 53 years) with metastatic triple-negative breast cancer receiving treatment at various U.S. and European academic medical centers between January 2013 and February 2016.
Patients received 15 mg/kg, 20 mg/kg or 1,200 mg flat-dose atezolizumab IV every 3 weeks until unacceptable toxicity or loss of clinical benefit.
Those eligible had measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, ECOG performance status of 0 to 1, and a representative tumor sample for assessment of immune cell PD-L1 expression.
Safety and tolerability served as primary endpoints. Secondary endpoints included objective response rate, duration of response and PFS. OS served as an exploratory endpoint.
Median follow-up was 25.3 months (range, 0.4-45.6 months).
Treatment-associated adverse events occurred among 63% of patients, of which 79% were grade 1 to grade 2. Most occurred within the first year of treatment.
The most common treatment-associated adverse events included pyrexia (16%), fatigue (13%), nausea (11%), diarrhea (10%), asthenia (10%) and pruritus (10%).
In all patients, median duration of response was 21 months by RECIST and 25 months by immune-related response criteria (irRC).
Researchers reported a median PFS of 1.4 months (95% CI, 1.3-1.6) by RECIST and 1.9 months (95% CI, 1.4-2.5) by irRC.
Among 115 evaluable patients, atezolizumab yielded an ORR by RECIST of 10% (95% CI,4.9-16.5). ORR reached 24% (95% CI,8.2-47.2) as among patients receiving first-line therapy and 6% (95% CI,2.4-13.4) for those receiving second-line therapy or greater.
By iRC, ORR was 13% (95% CI, 7.5-20.6) overall 24% (95% CI, 8.2-47.2) as first-line therapy and 11% (95% CI, 5.2-8.7). as second-line therapy.
Median OS was 8.9 months (95% CI, 7-12.6). OS was 41% (95% CI, 32-50) at 1 year, 19% (95% CI, 11-26) at 2 years and 16% (95% CI, 8-24) at 3 years (95% CI, 8-24).
PD-L1 expression of at least 1% tumor-infiltrating immune cells was associated with a higher ORR (12% vs. 0%) and longer OS (10.1 months vs. 6 months) compared with less than 1% tumor-infiltrating immune cells.
Researchers found levels of immune cells greater than 10% were independently associated with higher ORRs and longer OS.
Limitations of the study included its single-arm design and that enrollment initially was restricted to PD-L1-selected patients with metastatic triple-negative breast cancer but later broadened to all comers.
“Combination immunotherapies that add chemotherapy or other drugs to atezolizumab may increase the number of patients who benefit. This is now being evaluated in randomized clinical trials,” Emens said. – by Jennifer Southall
For more information:
Leisha A. Emens, MD, PhD, can be reached at University of Pittsburgh, UPMC Hillman Cancer Center, 5117 Centre Ave., Pittsburgh, PA 15213; email: firstname.lastname@example.org.
Disclosures: Emens reports research funding from AstraZeneca, Corvus, EMD Serono and Roche/Genentech; grants from Aduro Biotech, the Breast Cancer Research Foundation, Maxcyte and Merck; advisory board honoraria from Abbvie, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Celgene, eTHeRNA, Gritstone, MedImmune, Molecuvax, Peregrine, Replimune, Roche/Genentech, Syndax and Vaccinex; royalties from Aduro and Biotech; and stock options from Molecuvax. Please see the study for all other researchers’ financial disclosures.