Pembrolizumab-emerging treatment of pulmonary sarcomatoid carcinoma: A case report

BACKGROUND Few studies have addressed the efficacy of pembrolizumab in pulmonary sarcomatoid carcinoma(PSC),a rare,previously rapidly fatal subtype of nonsmall-cell lung cancer.CASE SUMMARY We report the case of a 69-year-old man presented with respiratory distress caused by a large left upper lung lobe mass diagnosed as PSC with programmed death-ligand 1 expressed on more than 50 percent of tumor cells.The patient was started on pembrolizumab and,after 5 cycles,there was a more than 80 percent decrease in the size of the tumor mass.Further decrease was seen at the end of 10 cycles.The patient has been tolerating pembrolizumab well,with no limiting side-effects.Fourteen months after first coming into the hospital,he remains asymptomatic.CONCLUSION Pembrolizumab appears as a viable emerging treatment for PSC.

Significant benefits of pembrolizumab in treating refractory advanced pulmonary sarcomatoid carcinoma: A case report

BACKGROUND Pulmonary sarcomatoid carcinoma(PSC),a rare subtype of non-small cell lung cancer(NSCLC),is poorly differentiated and highly aggressive.Treatment is limited,and the prognosis is poor.Pembrolizumab is an anti-programmed death(PD)-1 antibody with good efficacy in NSCLC.Recent studies have demonstrated that PD-ligand 1(PD-L1)overexpression is common in PSCs,which suggests that anti-PD-L1 treatment is an ideal option.However,the response to pembrolizumab in PSC has not been studied.CASE SUMMARY We present a PSC case with PD-L1 overexpression that significantly benefited from pembrolizumab.A 73-year-old Chinese male was detected with a right lung lesion.Pathological analysis of the right upper lobectomy confirmed PSC.The PDL1 test revealed overexpression(TPS:90%).Multiple metastases occurred 1 mo after surgery,representing stage IV PSC.Neither first-line chemotherapy nor second-line antiangiogenic agents showed any benefit.Radiotherapy(1200 cGy)was administered to relieve chest wall pain.The patient received the PD-1 inhibitor pembrolizumab(100 mg)as third-line therapy;however,because of fever and severe infection,he refused to receive immunotherapy any longer.Thus,only one dose of pembrolizumab was administered.Deep sustained remission of most of the metastases was achieved except for lesions in the right adrenal gland,which first shrank and then progressed.The patient died because of disease progression in the right adrenal gland.He achieved a progression-free survival time of 8 mo and an overall survival time of 9 mo with third-line pembrolizumab.CONCLUSION Our findings highlight and offer direct evidence of the efficacy of pembrolizumab in PD-L1-overexpressing PSCs.Combined radiotherapy and immunotherapy may enhance treatment efficacy.

Integrative genomic and transcriptomic profiling of pulmonary sarcomatoid carcinoma identifies molecular subtypes associated with distinct immune features and clinical outcomes

Background:Pulmonary sarcomatoid carcinoma(PSC)is a rare and aggressive subtype of non-small cell lung cancer(NSCLC),characterized by the presence of epithelial and sarcoma-like components.The molecular and immune landscape of PSC has not been well defined.Methods:Multiomics profiling of 21 pairs of PSCs with matched normal lung tissues was performed through targeted high-depth DNA panel,whole-exome,and RNA sequencing.We describe molecular and immune features that define subgroups of PSC with disparate genomic and immunogenic features as well as distinct clinical outcomes.Results:In total,27 canonical cancer gene mutations were identified,with TP53 the most frequently mutated gene,followed by KRAS.Interestingly,most TP53 and KRAS mutations were earlier genomic events mapped to the trunks of the tumors,suggesting branching evolution in most PSC tumors.We identified two distinct molecular subtypes of PSC,driven primarily by immune infiltration and signaling.The Immune High(IM-H)subtype was associated with superior survival,highlighting the impact of immune infiltration on the biological and clinical features of localized PSCs.Conclusions:We provided detailed insight into the mutational landscape of PSC and identified two molecular subtypes associated with prognosis.IM-H tumors were associated with favorable recurrence-free survival and overall survival,highlighting the importance of tumor immune infiltration in the biological and clinical features of PSCs.