medwireNews: Immune checkpoint inhibitors (ICIs) achieve high response rates and prolonged overall survival (OS) among patients with pulmonary sarcomatoid carcinoma when used in the second- or later-line, report researchers.
Marie Wislez (Hôpital Cochin, Paris, France) and team explain that pulmonary sarcomatoid carcinoma is a rare subtype of non-small-cell lung cancer that “is associated with tobacco use, resulting in a high mutation rate, with probably numerous neoantigens rendering patients highly immunogenic and, thus, good candidates for ICI.”
They evaluated the records of 32 patients, from 27 French centers, who received ICIs in the second- (n=54%) or later-line (n=46%) for stage III/IV disease between 2011 and 2017, with the majority (86.5%) receiving nivolumab.
As reported in the Journal of Thoracic Oncology, the objective response rate (ORR) was 40.5%, the disease control rate (DCR) was 64.8%, and the median progression-free survival (PFS) and overall survival (OS) durations were 4.9 and 12.7 months, respectively.
“These results appear to be superior to those observed with chemotherapy,” say the researchers, noting that historically chemotherapy has resulted in ORRs of 0–16.5% and median OS times of 5.0–7.7 months in these patients. Moreover, all study participants had previously received a median four cycles of platinum-based chemotherapy, which resulted in an ORR of 29.7% and DCR of 56.8%.
Further analysis of biomarkers revealed a trend towards better outcomes in patients with PD-L1 positivity (tumor proportion score ≥5%) and those with high tumor mutational burden (TMB; ≥10 mutations/Mb), but there was just one patient each in the PD-L1-negative and low TMB subgroups.
In total, six patients reported toxicities, three of whom discontinued treatment due to grade 2 autoimmune hepatitis and diarrhea in one case, grade 2 interstitial pneumonia and thyroiditis in the second case, and grade 2 interstitial pneumonia in the third case.
Discussing the results, the investigators caution that despite the favorable response rates observed, one-third of the study participants experienced progression prior to the first evaluation at 2 months. Though they were “unable to identify any characteristics predicting these early progressions,” Wislez et al think that PD-L1 expression is unlikely to be a predictor, as levels ranged from 0–100% among this group.
On the other hand, the researchers say they “cannot ignore” the fact that 40% of these early progression participants had a performance status of 2 or more, and acknowledge a trend towards higher efficacy and survival according to performance score, but again without reaching statistical significance.
Wislez and colleagues acknowledge that “[a] limitation of our work is the small number of patients enrolled due to the disease’s rarity, despite all ICI-treated patients from the 27 centers being consecutively included.”
And they conclude: “These data support the prospective investigation of ICI in [sarcomatoid carcinoma] patients in first-line treatment.”
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