A high response rate to immune checkpoint inhibitor (ICI) therapy was observed in patients with pretreated lung sarcomatoid carcinoma, according to results of a retrospective study published in the Journal of Thoracic Oncology.1

Lung sarcomatoid carcinoma is a rare subtype of non-small cell lung cancer (NSCLC) that represents less than 1% of all lung cancers, and is characterized by poorly differentiated carcinoma that also contains histologic features of sarcoma.

Compared with patients diagnosed with adenocarcinoma or squamous cell carcinoma of the lung, those with lung sarcomatoid carcinoma are more likely to experience early metastases, resistance to platinum-based chemotherapy, and a worse prognosis, with median overall survival [OS] reported to be in the range of 5 to 7.7 months.1-3 Hence, there is an unmet need for effective therapeutic approaches in this disease.

This study included 37 consecutive patients with advanced sarcomatoid carcinoma from 27 French centers who received ICI therapy in the second-line setting or beyond between 2011 and 2017.


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Over 94% of study patients had previously received first-line platinum-based chemotherapy for a median of 4 cycles of platinum. The objective response rate (ORR) following chemotherapy was 29.7%, although no patients achieved a complete response (CR).  

Median patient age was 63.2 years, and approximately three-quarters of patients were men. A median of 10 cycles of ICI therapy was administered in the second-line or higher-line settings in 54% and 46% of patients, respectively. Most patients (86.5%) received nivolumab, with the remainder treated with either pembrolizumab or atezolizumab.

The ORR to ICI therapy was 40.5%, with a disease-control rate of 64.8%, regardless of PD-L1 status. Median progression-free survival and median OS were 4.89 months and 12.7 months, respectively — however, disease progression within 2 months of treatment occurred in 32.4% of patients.

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Regarding toxicity, adverse events were reported in 16.2% of patients, and 3 patients discontinued treatment due to an immune-related adverse event.

Of the 19 samples evaluated for programmed cell death-ligand 1 (PD-L1) expression by immunohistochemistry, only 1 was classified as PD-L1–negative. Assessments of tumor mutational burden (TMB) using next-generation sequencing revealed a “TMB-high” (ie, more than 10 mutations/megabase) status for 7 of the 8 samples tested.

Although median OS was higher in the group of patients with tumors characterized by high level of expression PD-L1 or higher TMB compared with those with tumors with low PD-L1 expression or lower TMB, these differences were not statistically significant.

The study authors cited small sample size as a limitation of the study, but also concluded that “these data support the prospective investigation of ICI in [sarcomatoid carcinoma] patients in first-line treatment.”

Disclosures: Some of the authors disclosed financial relationships with pharmaceutical and medical device companies. For a full list of disclosures, please refer to the original study.

References

  1. Domblides C, Leroy K, Monnet I, et al. Efficacy of immune checkpoint inhibitors in lung sarcomatoid carcinoma [published online January 25, 2020]. J Thorac Oncol. doi: 10.1016/j.jtho.2020.01.014
  2. Maneenil K, Xue Z, Liu M, et al. Sarcomatoid carcinoma of the lung: The Mayo Clinic experience in 127 patients. Clin Lung Cancer. 2018;19(3):e323-e333.
  3. Karim NA, Schuster J, Eldessouki I, et al. Pulmonary sarcomatoid carcinoma: University of Cincinnati experience. Oncotarget. 2017;9(3):4102-4108.