Chemoimmunotherapy shows promise for untreated HER2-mutated advanced NSCLC
medwireNews: Combined treatment with immune checkpoint inhibitors (ICIs) and chemotherapy could be an option for treatment-naïve patients with advanced non-small-cell lung cancer (NSCLC) harboring HER2 alterations, suggests a chart review.
“Our data indicate that the efficacy of immune checkpoint inhibitors combined with platinum-based chemotherapy is likely similar in HER2-selected and -unselected NSCLC,” write the researchers in the Journal of Thoracic Oncology.
“This supports the status of these regimens as the current standard of care and benchmark for future comparative trials in previously untreated [HER2-mutated] NSCLC patients.”
The team identified 61 patients with stage III or IV disease and HER2 alterations (excluding gene amplifications) who received ICIs, either alone or alongside chemotherapy, within the German National Network Genomic Medicine Lung Cancer consortium between 2016 and 2020.
Participants were aged a median of 61 years at diagnosis, two-thirds had HER2 exon 20 insertions, and just under half (n=27) had not received prior treatment for advanced disease.
Among the 21 evaluable patients who received an ICI (pembrolizumab in all cases) plus chemotherapy in the first-line, the objective response rate (ORR) was 52%, median progression-free survival (PFS) was 6 months, and median overall survival (OS) was unreached at the time of analysis. The 1-year PFS and OS rates were 21% and 88%, respectively.
Two of the five individuals given ICI monotherapy (pembrolizumab in four, nivolumab in one patient) had early disease progression, while the remaining three had either a partial response or stable disease and were continuing treatment at 6, 18, and 26 months.
The two patients with durable benefit “can be seen as proof-of-principle cases showing that single-agent immunotherapy can also be effective in [HER2-mutated] NSCLC, but, surely, allow no definitive conclusions,” say Martin Wermke (Universitätsklinikum Carl Gustav Carus, Dresden, Germany) and colleagues.
They also evaluated the outcomes of the 34 participants treated with ICI monotherapy in the second- or later-line (nivolumab in 56%, pembrolizumab in 29%, and atezolizumab in 15%), and found that the ORR was 16%, while the median PFS and OS durations were 4 and 10 months, respectively. The PFS rate at 1-year was 12% and the OS rate was 36%.
These data are “similar to previously published results from HER2-selected and -unselected NSCLC cohorts,” but compare “unfavorably with early efficacy data of HER2-specific tyrosine kinase inhibitors or antibody drug conjugates, which have been associated with [an] ORR of 50% to 62% in this setting,” comment the researchers.
They note, however, that the study indicates that “[HER2-mutated] NSCLC might not be as insensitive to single-agent checkpoint blockade as patients with other driver mutations and supports the rationale of ongoing clinical trials combining checkpoint blockade with HER2-targeted therapy and chemotherapy.”
Acknowledging the limitations of their study, such as the retrospective nature and lack of central radiology review, Wermke et al observe that “longer follow-up and larger cohorts will be required to comprehensively evaluate the potential of ICI to induce long-term disease control in [HER2-mutated] NSCLC.”
But they add: “[G]iven the rarity of the disease and scarcity of available data, these results may still be of relevance to thoracic oncologists.”
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