Real-world effectiveness may not reflect trial efficacy for HER2-targeted agents
medwireNews: Women receiving first-line pertuzumab or second-line trastuzumab emtansine (T-DM1) for HER2-positive metastatic breast cancer have lower than expected survival times in clinical practice when compared with pivotal trials, researchers report.
Writing in JAMA Oncology, Josee-Lyne Ethier (Queen’s University, Kingston, Ontario, Canada) and co-authors suggest that the “differences in outcome likely reflect differences in patient population and previous lines of therapy in routine practice.”
Ethier and team found that median overall survival (OS) was 43 months in their real-world cohort of 795 women (median age 57 years) who received pertuzumab for first-line metastatic treatment between December 2013 and December 2017.
They note that women in this cohort, identified from the Ontario Cancer Registry, were similar to those in the CLEOPATRA study, in that they had not received prior trastuzumab for metastatic disease or within 12 months in the neoadjuvant setting.
Yet median OS in CLEOPATRA was substantially longer, at 57 months.
In addition, median time on pertuzumab, which the researchers say can be used as a surrogate for progression-free survival (PFS), was 14 months in in the current analysis, whereas median PFS in CLEOPATRA was 19 months.
They also note that each 10-year increase in age in the Ontario cohort was associated with a significant 30% increased risk for death, while receiving pertuzumab within 3 months of diagnosis – which may reflect de novo metastases – was associated with a 45% lower risk for death compared with a wait of more than 48 months.
And when the investigators adjusted the median age of their participants to 54 years, to approximate a population closer to that of CLEOPATRA, they found that the median OS was 53 months.
They say: “This exploratory analysis suggests that the observed efficacy-effectiveness gap in outcomes of treatment with pertuzumab is largely driven by differences in patient age between routine practice and the clinical trial.”
Ethier et al also looked at data for 506 individuals who received T-DM1, the majority of whom had received prior treatment with trastuzumab in the metastatic setting either alone (34.6%) or in combination with pertuzumab (63.8%).
The median OS in this group was 15 months and the median time on treatment was 4 months. However, the researchers found that median OS was significantly shorter for patients with versus without prior pertuzumab treatment, at 12 and 19 months, respectively.
By comparison, median OS in the experimental arm of the EMILIA trial was 30 months, but Ethier and team note that at the time of that trial, “pertuzumab was not approved for use in the metastatic setting.”
They comment: “This suggests that results from EMILIA may not be fully generalizable to current practice where standard of care includes treatment with first-line pertuzumab because patients with prior receipt of pertuzumab had shorter time on treatment and survival compared with the pertuzumab-naive subgroup.”
In spite of this, the authors stress that their “findings do not invalidate the results of large randomized clinical trials such as CLEOPATRA and EMILIA. Rather, they reflect outcomes associated with use of novel drugs in real-word circumstances.”
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