Immune-Checkpoint Inhibitors in Advanced Non-Small Cell Lung Cancer With Uncommon Histology

Manglaviti, Sara; Brambilla, Marta; Signorelli, Diego; Ferrara, Roberto; Russo, Giuseppe Lo; Proto, Claudia; Galli, Giulia; Toma, Alessandro De; Occhipinti, Mario; Viscardi, Giuseppe; Beninato, Teresa; Zattarin, Emma; Bini, Marta; Lobefaro, Riccardo; Massa, Giacomo; Bottiglieri, Achille; Apollonio, Giulia; Sottotetti, Elisa; Mauro, Rosa Maria Di; Trevisan, Benedetta; Ganzinelli, Monica; Fabbri, Alessandra; Braud, F.G.M. De; Garassino, Marina Chiara; Prelaj, Arsela

doi:10.1016/j.cllc.2021.06.013

Cited by 10 publications

(9 citation statements)

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“… 37 , 38 , 39 , 40 Furthermore, uncommon histological type of adenocarcinoma such as invasive mucinous adenocarcinomas and enteric adenocarcinomas frequently exhibited TTF‐1 negative status and those cancers are known to be less responsive to ICI. 41 , 42 , 43 Although the present study did not assess the KEAP1 and/or STK11 gene alterations and the detailed types of adenocarcinomas, above‐mentioned reports might partially explain why TTF‐1 negative lung adenocarcinoma showed worse outcomes with ICI monotherapy in our study. Few reports have suggested the mechanism of correlation between TTF‐1 and PD‐L1.…”

Section: Discussionmentioning

confidence: 67%

“…In preclinical models, TTF‐1 negativity is associated with loss of serine–threonine kinase 11 (STK11), which also negatively correlates with ICI effectiveness 37–40 . Furthermore, uncommon histological type of adenocarcinoma such as invasive mucinous adenocarcinomas and enteric adenocarcinomas frequently exhibited TTF‐1 negative status and those cancers are known to be less responsive to ICI 41–43 . Although the present study did not assess the KEAP1 and/or STK11 gene alterations and the detailed types of adenocarcinomas, above‐mentioned reports might partially explain why TTF‐1 negative lung adenocarcinoma showed worse outcomes with ICI monotherapy in our study.…”

Section: Discussionmentioning

confidence: 76%

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Association of thyroid transcription factor‐1 with the efficacy of immune‐checkpoint inhibitors in patients with advanced lung adenocarcinoma

Nakahama

Osawa²,

Izumi

et al. 2022

Thoracic Cancer

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Background We aimed to identify the relationship between thyroid transcription factor‐1 (TTF‐1) expression of lung adenocarcinoma and the efficacy of immune‐checkpoint inhibitor (ICI) therapy. Methods This retrospective multicenter study comprised patients with advanced lung adenocarcinoma treated with ICI monotherapy. We collected clinical medical records including data on TTF‐1 expression and analyzed the relationship between TTF‐1 expression and programmed death‐ligand 1 tumor proportion score (PD‐L1 TPS), objective response rate (ORR), progression‐free survival (PFS), and overall survival (OS). Results In total, 108 patients with lung adenocarcinoma were analyzed. The rate of TPS ≥1% and ≥50% in patients with positive TTF‐1 expression was significantly higher than that in patients with negative TTF‐1 expression (88% vs. 60%, p < 0.001; 65% vs. 24%, p < 0.001). The ORR was significantly higher in TTF‐1 positive patients than in TTF‐1‐negative patients (38% vs. 8%, p = 0.003). Among patients with TPS ≥50% and 1%–49%, the ORR in TTF‐1 positive and negative patients was 48% (26/54) versus 17% (1/6) ( p = 0.21), and 32% (6/19) versus 11% (1/9) ( p = 0.37), respectively. The ORR for patients with TPS <1% was 0% in both the TTF‐1 negative and positive cases. The median PFS and OS was significantly longer in TTF‐1‐positive patients than in TTF‐1‐negative patients (5.4 vs. 1.6 months, p < 0.001; 18.2 vs. 8.0 months, p = 0.041). Multivariate analysis revealed that TTF‐1‐negative status was an independent unfavorable prognostic factor for PFS. Conclusion Patients with TTF‐1‐positive status receiving ICI monotherapy showed better outcomes than those with TTF‐1‐negative lung adenocarcinoma.

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Section: Discussionmentioning

confidence: 67%

Section: Discussionmentioning

confidence: 76%

Association of thyroid transcription factor‐1 with the efficacy of immune‐checkpoint inhibitors in patients with advanced lung adenocarcinoma

Nakahama

Osawa²,

Izumi

et al. 2022

Thoracic Cancer

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“…Among 19 patients with available samples for PD-L1 detection, only one was PD-L1 negative; the ORR was 58.8% in PD-L1+ patients and 0% in the single PD-L1− patient; a trend toward better OS was also observed in PD-L1+ patients, but there was no statistical significance [83]. In another retrospective study conducted by Manglaviti et al, 19 patients with metastatic sarcomatoid carcinoma were treated with ICIs; the achieved ORR was 31.6% (6/19), DCR was 36.8% (7/19), median PFS was 2.3 months, and median OS was 3.5 months [84]. In a pooled analysis that included the abovementioned 2 studies, Babacan et al found that PD-L1 expression is significantly associated with favorable tumor responses and PFS after checkpoint inhibitor immunotherapy; among patients with available tissue for PD-L1 detection, partial or complete response was achieved in 70.2% (33/47) of the patients with high PD-L1 expressions (≥50%), compared with 50% (5/10) of patients with a PD-L1 of 1%-49% and 28.6% (2/7) of patients with PD-L1 <1% (P � 0.026); PFS was longer among patients with PD-L1≥1%, compared with those with PD-L1 <1% (14.4 months versus 2.7 months, P � 0.04) [78].…”

Section: Efficacy Of Icis In Pscmentioning

confidence: 97%

Multimodality Treatment of Pulmonary Sarcomatoid Carcinoma: A Review of Current State of Art

Zhang

Lin

Yang

et al. 2022

Journal of Oncology

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Pulmonary sarcomatoid carcinoma (PSC) is an unconventional non-small-cell lung cancer (NSCLC) that is currently managed under guidelines used for conventional NSCLC and has poor survival. Surgery is the optimal choice for resectable PSC, and the prevalence of mutations in this type of tumor laid the foundation for novel systemic therapies such as targeted therapy and immunotherapy. PSC is resistant to chemotherapy and radiotherapy, and the effects of the 2 therapies are controversial. Targeted therapies have been reported to confer survival benefits, and savolitinib, an oral selective MET tyrosine-kinase inhibitor, has been approved in metastatic patients with MET exon 14 skipping mutations. Expression and positive rate of programmed death ligand 1 in PSC are high; our previous research has also revealed a high mutational burden and a T-cell-inflamed microenvironment of PSC. Correspondingly, immune checkpoint inhibitors have shown preliminary antitumor effects (overall response rates of 40.5% (15/37) and 31.6% (6/19) in two retrospective studies, respectively) in PSC patients. In summary, patients should receive operations at an early stage and multimodality treatments are needed to maximize the benefits of patients with advanced disease.

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“…It has previously been shown that PSC has a high tumor mutational burden and a T-cell-inflamed microenvironment. Two retrospective studies have shown preliminary antitumor effects of ICIs in patients having PSC with overall response rates of 40.5% (15/37) and 31.6% (6/19), respectively ( 13 , 30 ).…”

Section: Questions To Be Further Discussed and Consideredmentioning

confidence: 99%

Anlotinib combined with chemotherapy and immunotherapy for advanced pulmonary sarcomatoid cancer: a case report and literature review

Piao¹,

Ma²,

Tankere³

et al. 2022

Ann Transl Med

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Background: Pulmonary sarcomatoid carcinoma (PSC) is a rare disease which is highly malignant with a poor prognosis. PSC is highly resistant to chemotherapy and radiotherapy and is prone to recurrence even after surgery. Most of what is known about PSC comes from limited single-center, retrospective studies.There is still no standard international clinical guideline for PSC. Limited case reports have shown that PSC patients with driver gene mutations and high programmed death-ligand 1 (PD-L1) expression have good responses to molecular targeted therapy and immune checkpoint inhibitor (ICI) immunotherapy, respectively. Therefore, current first-line chemotherapy, targeted therapy and immunotherapy play a leading role in the diagnosis and treatment of advanced PSC patients.Case Description: We report a 42-year-old male who was diagnosed with PSC [stage IVB (T4N2M1)] and treated at our department (

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Immune-Checkpoint Inhibitors in Advanced Non-Small Cell Lung Cancer With Uncommon Histology

Cited by 10 publications

References 50 publications

Association of thyroid transcription factor‐1 with the efficacy of immune‐checkpoint inhibitors in patients with advanced lung adenocarcinoma

Association of thyroid transcription factor‐1 with the efficacy of immune‐checkpoint inhibitors in patients with advanced lung adenocarcinoma

Multimodality Treatment of Pulmonary Sarcomatoid Carcinoma: A Review of Current State of Art

Anlotinib combined with chemotherapy and immunotherapy for advanced pulmonary sarcomatoid cancer: a case report and literature review

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