e21074 Background: SMARCA4-deficient thoracic sarcomatoid tumors (SD-TSTs) is a rare and highly aggressive disease that lack clear treatment guidelines. This research reports the clinicopathological features of SD-TSTs and the promising efficacy of immune-checkpoint inhibitor with chemotherapy in SD-TSTs. Methods: A total of 16 patients were diagnosed and treated with SD-TSTs in Fudan University Shanghai Cancer Center (FUSCC) from January, 2017 to December, 2021. Clinicopathologic, genomic characteristics and treatment information were obtained and analyzed. Results: SD-TSTs were diagnosed at median age of 64.5 years old, and predominantly affected male (100%) with heavier smoking history (≥20 pack-year). Many patients were diagnosed at advanced stages (Stage I 18.8%, Stage II 25%, Stage III 25% and Stage IV 43.8%). The most often metastatic sites were adrenal gland, lymph nodes, bone and liver, while brain metastasis was not found. For patients underwent radical therapy, median disease-free survival is 4.8 months, indicating a rapid relapse pattern even for early-stage patients. 8 patients with Stage IV SD-TSTs were treated in FUSCC. As for first-line therapy, 3 patients received chemotherapy, whose regimen included gemcitabine plus cisplatin, doxorubicin plus ifosfamide, and vincristine, doxorubicin plus cyclophosphamide alternating with ifosfamine and etoposide. 5 patients received immune-checkpoint inhibitor plus chemotherapy as first-line therapy, including 3 patients treated with pembrolizumab plus nab-paclitaxel and carboplatin, 1 patient treated with tislelizumab plus nab-paclitaxel and carboplatin and 1 patient treated with sintilimab plus paclitaxel and carboplatin. Median progression-free survival (PFS) of first line was 6.53 months for all patients. First-line median PFS was significantly higher for patients with immune-checkpoint inhibitor plus chemotherapy than those treated with only chemotherapy (not reach vs. 2.73 months, p = 0.07). This result suggested that SD-TSTs were irresponsive to chemotherapy, including those used for sarcomas, and better responded to immune-checkpoint inhibitor included regimen. Conclusions: SD-TSTs is a highly aggressive disease. Immune-checkpoint inhibitor combined with chemotherapy showed promising efficacy in metastatic SD-TSTs than traditional chemotherapy. Considering the low incidence of SD-TSTs, our research contains the largest sample size by far to report the efficacy of immune-checkpoint inhibitor plus chemotherapy in this deadly disease.
Cisplatin (DDP) is a common therapeutic option for non‐small cell lung carcinoma (NSCLC). However, some patients fail to respond to the DDP chemotherapy. Therefore, identifying novel biomarkers to improve the diagnosis and treatment of NSCLC is important. Ubiquitin‐specific protease (USP14) is involved in various pathological conditions including cancer; however, the role of USP14 in NSCLC remains elusive. The SELEX technology was used to identify aptamers that specifically recognize DDP‐resistant lung cancer cells and couple them with nano‐zinc (zinc hydroxide, Zn(OH)2) carriers. USP14 levels were higher in DDP‐resistant lung cancer compared to DDP‐sensitive lung cancer. The survival rate of lung cancer patients with increased USP14 expression was significantly lower than the survival rate of patients with low USP14 expression. Silencing USP14 increased the tumor antagonistic action of DDP in A549 cisplatin‐resistant (A549/DDP) cells, while USP14 overexpression decreased the antagonist effects. Aptamer‐targeted nano‐zinc carriers were loaded with USP14 siRNA to target DDP‐resistant lung cancer cells. Aptamer‐targeted nano‐zinc carriers containing USP14 siRNA increased the antitumor effects of DDP in A549/DDP cells and mice bearing A549/DDP cells. These results indicate that aptamer‐guided nano‐zinc carriers may be a potent carrier for the precise treatment of drug‐resistant tumors.
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e21029 Background: Currently neither chemotherapy nor approved EGFR TKIs have satisfactory efficacy in most EGFR 20ins mutations. Activity of high-dose furmonertinib, a novel 3rd generation EGFR TKI, against EGFR 20ins was assessed in preclinical models and a phase lb study. This study aimed to retrospectively investigate the efficacy of high-dose furmonertinib against EGFR 20ins in the real world. Methods: Retrospective search identified 14 metastatic NSCLC patients (pts) with EGFR 20ins treated with high-dose furmonertinib (160mg qd) in Fudan University Shanghai Cancer Center. The clinical efficacy and safety were investigated. Results: Median age was 60 years old (range 40-75) in this cohort with 28% female. At data cutoff date of January, 2022, 9 pts had ≥1 disease assessment. 5 out of 9 pts achieved PR, and 3 patients achieved SD. No CR was observed and 1 patient PD at first assessment. The most common adverse events (AE, ≥20%) were diarrhea, paronychia, skin fissures, anorexia, pain in extremity, rash and stomatitis. No grade ≥3 AE was observed. Conclusions: High-dose furmonertinib has shown encouraging anti-tumor activity in NSCLC with EGFR 20ins.
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