Early atezolizumab results point to potential role in metastatic TNBC care
medwireNews: Phase I trial findings suggest that patients with metastatic triple-negative breast cancer (mTNBC) might benefit from treatment with the programmed cell death ligand 1 (PD-L1) inhibitor atezolizumab.
“Single-agent atezolizumab was well tolerated and provided durable clinical benefit in patients with mTNBC with stable or responding disease and in earlier lines of treatment”, the investigators write in JAMA Oncology.
The first-in-human PCD4989g study of atezolizumab monotherapy for solid and haematological malignancies included 116 women, aged a median of 53 years, with metastatic TNBC treated between January 2013 and February 2016.
Open-label atezolizumab was given on a 3-week schedule; the majority (n=93) of participants received a flat dose of 1200 mg, while 22 patients were given atezolizumab 15 mg/kg and one patient 20 mg/kg. Patients received a median of four cycles of atezolizumab over a median of 2.1 months.
Safety analysis revealed that treatment-related adverse events (TRAEs) occurred in 63% of patients, and 79% of side effects were classified as grade 1 or 2 in severity. In all, 11% of patients experienced grade 3 or 4 TRAEs, including grade 3 pruritic rash, lichen planus and adrenal insufficiency, and grade 4 pneumonitis.
There were two grade 5 TRAEs, namely one case of pulmonary hypertension and another listed as death not otherwise specified.
Leisha Emens (University of Pittsburgh, Pennsylvania, USA) and co-authors used both Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST) and immune-related response criteria (irRC) to assess disease response to treatment.
Overall, 21 patients were given atezolizumab as a first-line treatment for mTNBC and these individuals had a numerically higher objective response rate (ORR) than the 94 patients who had received at least one prior treatment. This was true when measured by both RECIST (24 vs 6%) and irRC (24 vs 11%).
The disease control rate was 13% using RECIST and 17% with irRC; four patients were classified as responding to treatment using irRC but had disease progression or stable disease on RECIST.
Median progression-free survival by RECIST and irRC was 1.4 and 1.9 months, respectively. Median overall survival was 17.6 months with first-line atezolizumab, falling to 7.3 months for those given the agent as a second or subsequent therapy.
Moreover, patients with PD-L1 expression of at least 1% in tumour-infiltrating immune cells had a higher ORR than those without this level of expression (12 vs 0%), and better median overall survival (OS; 10.1 vs 6.0 months).
And in multivariable analysis, an immune cell level greater than 10% independently predicted better outcomes in terms of ORR, irRC-based progression-free survival and OS, the researchers add.
Noting that mTNBC is associated with a poor prognosis, Leisha Emens and team comment that the median OS achieved with atezolizumab in the study is “comparable to that with standard chemotherapy, without the AEs typical of chemotherapy.”
Hypothesizing that “[c]ombination immunotherapy strategies, which may increase ORR and prolong the survival of more patients with mTNBC, could change the treatment paradigm for this disease”, they highlight that the phase III Impassion130 trial is now underway to assess atezolizumab with nab-paclitaxel in treatment-naïve mTNBC.
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