The efficacy and safety analysis of first-line immune checkpoint inhibitors in pulmonary sarcomatoid carcinoma

Abstract

BackgroundPulmonary sarcomatoid carcinoma (PSC) is a rare and aggressive disease without standardized treatment strategies. The efficacy of second-line or beyond immune checkpoint inhibitors (ICIs) has been proven in recent studies, whereas the evidence for first-line immunotherapy for PSC is still limited to case reports and remains poorly understood.Materials and methodsThis was a multicenter, retrospective analysis of 21 patients with a histological diagnosis of PSC who received ICI as first-line therapy from January 2019 to March 2022. The expression of PD-L1 was evaluated by immunohistochemistry (IHC) using the monoclonal antibody 22C3. Low and high PD-L1 expressions were defined using the tumor proportion score (TPS), with cutoffs of 1 and 50%, respectively.ResultsAll eight patients had PD-L1 positivity who underwent PD-L1 expression assessment, and six patients (6/8, 75.0%) had high PD-L1 expression. Among the 21 PSC patients, seven received tislelizumab, six received camrelizumab, four received sintilimab, three received pembrolizumab, and one received durvalumab. Among them, 18 PSCs received combination therapy, whereas another three PSCs received immunotherapy alone. Out of the 21 PSC patients, 12 (57.1%) achieved a partial response (PR), and five patients had stable disease (SD) as the best response, whereas four PSCs experienced dramatic progressive disease (PD). The median progression-free survival (PFS) was 9.2 (95% CI [4.3, 14.1]) months, and the median OS was 22.8 (95% CI [4.0, 41.5]) months. Among the three treatment groups (immunotherapy alone, immunotherapy combined with anlotinib, and chemoimmunotherapy), the median PFS was 8.0, 9.4, and 9.6 months, and the median OS was 19.0, 22.8, and 30.6 months, respectively. There was no difference in PFS and OS between the three treatment regimen groups (P = 0.86 and P = 0.34, respectively) and different immunotherapies (P = 0.10 and P = 0.23, respectively). No serious adverse events (grade ≥ 3) were noted.ConclusionFirst-line immunotherapy has promising therapeutic potential in the treatment of PSC. More studies are warranted to confirm these findings.

Role of immunotherapy in pulmonary sarcomatoid carcinoma: review of current approaches and related biomarkers

“…Besides, no serious TRAEs (grade ⩾3) were noticed. 15 Matsumoto et al 16 reported a case with advanced PSC who received pembrolizumab monotherapy as first-line treatment and achieved a partial response (PR) after three treatment cycles with an acceptable safety profile.…”

“…Importantly, both regimens were generally well tolerated. 15 Furthermore, Li et al 20 reported a case of advanced PSC switched to tislelizumab plus anlotinib therapy after failure of first-line conventional chemotherapy, and after 13 cycles of the combined treatment, the patient achieved complete response (CR) and was still on the drug.…”

“…TRAEs of grade ⩾3 were not found. 15 Okauchi et al presented a case report of a 60-year-old male with advanced primary PSC characterized by high PD-L1 expression (TPS >75%). This patient was treated with pembrolizumab in combination with platinum-based chemotherapy, and after six cycles of the combined therapy, the patient achieved a significant general remission with a PR by the efficacy assessment and experienced no significant TRAEs.…”

Biological characteristics and clinical treatment of pulmonary sarcomatoid carcinoma: a narrative review

“…Regarding the impact of first-line immunotherapy on patients with PSC, a multicenter retrospective study enrolled 21 patients with PSC receiving first-line immunotherapy ( 161 ). Of these patients, 14 received immunotherapy combined with anlotinib (tislelizumab: 7; camrelizumab: 4; sintilimab: 2; pembrolizumab: 1), 4 received immunotherapy combined with platinum-based chemotherapy (pembrolizumab: 2; sintilimab: 1; durvalumab: 1), and 3 patients received immune monotherapy (camrelizumab: 2; sintilimab: 1) ( 161 ). The ORR was 57.1%, the disease control rate (DCR) was 81% (PR: 12; SD: 5; PD: 4), the median PFS was 9.2 months, and the median OS was 22.8 months ( 161 ).…”

The functional network of biglycan: A new frontier in tumor progression

“…26 Neutrophil extracellular traps (NETs) are network structures released from activated neutrophils. NETs promote tumor metastasis by inducing epithelial-mesenchymal transition in non-small-cell lung cancer, 68 gastric cancer, 69 and CRC. 70 In addition, NETs shield tumor cells from clearance by immune cells, resulting in increased tumor growth.…”