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1.
BMC Cancer ; 23(1): 16, 2023 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-36604688

RESUMEN

BACKGROUND: Antiangiogenic drugs have shown initial efficacy in the treatment of advanced thymic carcinomas (TCs); however, data are limited. In this study, we provide real-world data relating to the efficacy of antiangiogenic drugs for the treatment of patients with TCs. METHODS: We retrospectively collected data on clinical progress after first-line chemotherapy in TCs patients who were treated with small molecule antiangiogenic drugs at our institution between January 2010 and December 2021. Tumor response was evaluated according to version 1.1 of the Response Evaluation Criteria in Solid Tumors. Progression free survival and overall survival were calculated using the Kaplan-Meier method. RESULTS: Of the 17 patients enrolled, 13 (76.5%) received apatinib and four (23.5%) anlotinib monotherapy with an objective response rate of 23.5%. Eleven (64.7%) patients had stable disease. The median follow-up period was 46.0 months (95% confidence interval [CI], 33.0-59.0 months). The median progression survival and overall survival were 7.9 months (95% CI, 6.5-9.3) and 47.0 months (95% CI, 35.4-58.6), respectively. In the 13 patients receiving apatinib, the median PFS was 7.0 months (95% CI, 5.0-9.0), compared with 8.0 months (95% CI, 2.7-13.3 months) for patients in the anlotinib group (P = 0.945). The most common grade 3 adverse events (AEs) were hypertension (n = 3, 23.1%), followed by proteinuria and hand-foot syndrome (HFS, n = 2, 15.4%). There were no grade 4 AEs although eight patients (47.1%) required mid-course discontinuation. CONCLUSION: For refractory TCs, small molecule antiangiogenic drugs are efficacious as second- or post-line treatments. The toxicity of antiangiogenic therapy is manageable.


Asunto(s)
Antineoplásicos , Neoplasias Pulmonares , Timoma , Neoplasias del Timo , Humanos , Inhibidores de la Angiogénesis/efectos adversos , Antineoplásicos/uso terapéutico , Timoma/tratamiento farmacológico , Estudios Retrospectivos , Neoplasias Pulmonares/patología , Neoplasias del Timo/tratamiento farmacológico
2.
BMC Pulm Med ; 23(1): 158, 2023 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-37147602

RESUMEN

BACKGROUND: We aimed to determine the clinical. outcomes of various immune checkpoint inhibitor (ICI) combinations for the treatment of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations. The results predicted the treatment efficacy of these combinations. METHODS: From July 15, 2016 to March 22, 2022, 85 NSCLC patients with EGFR mutations, enrolled at the Zhejiang Cancer Hospital, received ICI combinations after resistance to prior EGFR-tyrosine kinase inhibitors (EGFR-TKIs). These patients were diagnosed with EGFR mutations using an amplification refractory mutation system PCR (ARMS-PCR) and next-generation sequencing (NGS). Survival times were analyzed using the Kaplan-Meier method and log-rank test. RESULTS: Patients who received ICIs combined with anti-angiogenic therapy had longer progression-free survival (PFS) and overall survival (OS) than patients who received ICIs combined with chemotherapy. There was no significant difference in survival time between patients who received ICIs combined with chemotherapy and anti-angiogenic therapy and patients who received ICIs combined with anti-angiogenic therapy or ICIs combined with chemotherapy, which was due to the limitation sample size of patients who received ICIs combined with chemotherapy and anti-angiogenic therapy. Patients with L858R mutations had a longer PFS and OS than patients with exon 19 deletions. T790M negative patients benefited more from ICI combinations, compared with T790M positive patients. In addition, there was no significant difference in PFS and OS between patients with TP53 co-mutations and patients without a TP53 co-mutation. We also found that patients with prior first-generation EGFR-TKI resistance had longer PFS and OS than prior third-generation EGFR-TKI resistance patients. There was no new adverse event in this study. CONCLUSIONS: EGFR-mutated patients who received ICIs combined with anti-angiogenic therapy had longer PFS and OS than patients with ICIs combined with chemotherapy. Patients with L858R or without T790M mutation benefited more from ICI combinations. Besides, patients with prior first-generation EGFR-TKI resistance could benefit more from ICIs combinations than prior third-generation EGFR-TKI resistance patients.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Receptores ErbB/genética , Mutación , Inhibidores de Proteínas Quinasas/efectos adversos
3.
Genes Chromosomes Cancer ; 61(9): 530-541, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35396765

RESUMEN

The incidence of primary and acquired BRAF mutations is low in non-small cell lung cancer (NSCLC), with limited demographic and treatment outcome data available for this patient population. We evaluated lung cancer samples with programmed cell death ligand 1 (PD-L1) information extracted from 12 051 cases (cohort A) of lung cancer from OncoPanscan™-based sequencing of tissue (Genetron Health) and conducted retrospective multicenter data analysis using the database of Zhejiang Cancer Hospital and four other centers (cohort B, including 73 primary BRAF mutation and 14 acquired BRAF mutation cases) to compare treatment outcomes of patient groups with primary and acquired BRAF mutations. In cohort A, after propensity score analysis, 165 samples of NSCLC with BRAF mutations were screened along with 165 paired non-BRAF mutation samples. We observed no significant differences in the proportion of samples with ≥1% PD-L1 between BRAF and non-BRAF mutant groups. The median progression-free survival (mPFS) period in 13 patients with primary BRAF mutations receiving BRAF tyrosine kinase inhibitors (BRAF-TKIs) was 7.0 months. The group with primary BRAF mutations receiving immune checkpoint inhibitor (ICI) combination chemotherapy had better PFS than those administered ICI monotherapy (14.77 months vs. 5.0 months, p = 0.025) and similar results were obtained for OS (unreached vs. 20.3 months, p = 0.013). For acquired BRAF mutations, mPFS of BRAF-TKI, ICI-based, and chemotherapy-based regimens were 3.8, 1.5, and 1.9 months, respectively. Therefore, for patients with the primary BRAF V600E mutation, targeted therapy or immunochemotherapy could serve as effective treatment choices, while for those with acquired BRAF V600E, targeted drug therapy may remain the preferred solution in China.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Antígeno B7-H1/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Mutación , Proteínas Proto-Oncogénicas B-raf/genética , Estudios Retrospectivos , Resultado del Tratamiento
4.
Neoplasma ; 69(4): 976-982, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35603955

RESUMEN

We aimed to explore the treatment efficacy of first-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for lung squamous cell carcinoma (SCC) patients and identify potential beneficial subgroups of EGFR-mutated lung SCC patients in this study. Between February 1st, 2013 and December 1st, 2021, 657 advanced lung SCC patients were enrolled at Zhejiang Cancer Hospital. Amplification refractory mutation system PCR or next-generation sequencing were used to detect gene abnormality. Clinicopathological features were analyzed by chi-square test and the clinical results of lung SCC patients who received first-generation EGFR-TKI were analyzed by the Kaplan-Meier method. Lung SCC patients harboring EGFR mutation accounted for 11.0% in this study. Of 657 lung SCC patients, the median PFS and OS of 116 patients who received targeted therapy were 3.6 months and 16.2 months, patients treated with targeted therapy had similar OS to patients without targeted therapy (p=0.839). Of 110 lung SCC patients who received first-generation EGFR-TKI, EGFR-mutated patients had long PFS (p=0.000) but similar OS (p=0.472) than patients with EGFR wide type. EGFR-mutated SCC patients who received first-generation EGFR-TKI as a first-line benefit are equal to patients who received first-generation EGFR-TKI as the second line or beyond according to similar PFS (p=0.311) and OS (p=0.721) between them. In addition, there was also no significant difference in PFS (p=0.376) and OS (p=0.205) between patients with exon 19 deletion and L858R point mutation. Lung SCC patients harboring EGFR mutation received first-generation EGFR-TKI had better clinical survival than patients with EGFR wide type.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Células Epiteliales , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Mutación , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Estudios Retrospectivos
5.
BMC Pulm Med ; 22(1): 381, 2022 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-36253772

RESUMEN

BACKGROUND: Anemia is relatively common in cancer patients, and baseline anemia is associated with poor survival in patients with non-small cell lung cancer (NSCLC). However, there is a lack of large-sample studies of patients with NSCLC with epidermal growth factor receptor (EGFR) mutations. METHODS: We retrospectively analyzed anemia­related data for patients with NSCLC and EGFR mutations who were admitted to Zhejiang Cancer Hospital from January 2013 to June 2019 and treated with targeted therapy. The patients' clinicopathological features were evaluated by χ2 tests and the relationships between clinical characteristics and prognosis were investigated using Kaplan-Meier and multivariate Cox regression analyses. RESULTS: A total of 2,029 patients treated with EGFR-tyrosine kinase inhibitors (TKIs) were finally enrolled in this study, of whom 24.6% had baseline anemia. Patients without baseline anemia had longer median overall survival (OS) than patients with baseline anemia (36.10 vs. 29.10 months, P = 0.001), and patients with grade < 2 anemia had longer median OS than those with grade ≥ 2 anemia (35.00 vs. 25.10 months, P < 0.001). Multivariate analyses identified baseline anemia as a factor predicting a poor prognosis in terms of OS in patients with EGFR mutations. CONCLUSIONS: Baseline anemia is a significant factor predicting a poor prognosis in terms of OS in patients with NSCLC and EGFR mutations treated with targeted therapy. A higher grade of baseline anemia may also be related to shorter OS. And a higher risk of EGFR-mutated patients who had received targeted therapy could also be observed.


Asunto(s)
Anemia , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Anemia/genética , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Mutación , Pronóstico , Inhibidores de Proteínas Quinasas/uso terapéutico , Estudios Retrospectivos , Resultado del Tratamiento
6.
Cancer Med ; 12(15): 15903-15911, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37306192

RESUMEN

BACKGROUND: The efficacy of definite for non-small-cell lung cancer (NSCLC) with uncommon epidermal growth factor receptor (EGFR) mutations has been preliminarily demonstrated. However, there is a paucity of data with which to compare the efficacy and safety of second- and third-generation TKIs in patients with NSCLC carrying uncommon EGFR mutations. METHODS: We compared the efficacy and safety of second- and third-generation TKIs in all NSCLC patients in whom next-generation sequencing confirmed uncommon EGFR mutations, including G719X, S768I, and L861Q. The parameters analyzed included the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). The rate of treatment-related adverse events (AEs) reflected the safety of these TKIs. RESULTS: Eighty-four NSCLC patients with uncommon EGFR mutations were enrolled between April 2016 and May 2022 at Zhejiang Cancer Hospital, including 63 treated with second-generation TKIs and 21 treated with third-generation TKIs. The ORR for all patients receiving TKIs was 47.6%, and the DCR was 86.9%. The median PFS for NSCLC patients with uncommon EGFR mutations receiving TKIs was 11.9 months and OS was 30.6 months. There was no significant difference in PFS after treatment with second- or third-generation TKIs (13.3 vs. 11.0 months, respectively, P = 0.910) or in OS (30.6 vs. 24.6 months, respectively P = 0.623). The third-generation TKIs showed no severe toxicity. CONCLUSIONS: The efficacy of second- and third-generation TKIs for NSCLC with uncommon EGFR mutations does not differ, and so can be used to treat NSCLC patients with these mutations.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Inhibidores de Proteínas Quinasas/efectos adversos , Resultado del Tratamiento , Receptores ErbB/genética , Mutación
7.
J Thorac Dis ; 15(4): 1648-1657, 2023 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-37197488

RESUMEN

Background: Immunotherapy, monotherapy, and immunotherapy plus platinum-based chemotherapy are the standard treatments for advanced non-small cell lung cancer (NSCLC) patients with negative driver genes. However, the impact of similar continuing immunotherapy beyond progression (IBP) of first-line immunotherapy for advanced NSCLC has not yet been shown. This study aimed to estimate the impact of immunotherapy beyond first-line progression (IBF) and evaluate the factors associated with second-line efficacity. Methods: Ninety-four cases of advanced NSCLC patients with progressive disease (PD) post first-line treatment with platinum-based chemotherapy plus immunotherapy and administrated prior immune checkpoint inhibitors (ICIs) between November 2017 and July 2021 were retrospectively analyzed. Survival curves were plotted using the Kaplan-Meier method. Cox proportional hazards regression analyses were applied to determine predictive factors independently associated with second-line efficacity. Results: A total of 94 patients were incorporated in this study. Patients who continued the original ICIs after initial PD were defined as IBF (n=42), whereas those who discontinued immunotherapy were defined as non-IBF (n=52). The second-line objective response rates (ORR, ORR = CR + PR) of patients in the IBF and non-IBF groups were 13.5% vs. 28.6%, respectively (P=0.070). No significant survival difference was found between patients in the IBF and non-IBF groups in first-line median progression-free survival (PFS) (mPFS1, 6.2 vs. 5.1 months, P=0.490), second-line median PFS (mPFS2, 4.5 vs. 2.6 months, P=0.216), or median overall survival (OS) (mOS, 14.4 vs. 8.3 months, P=0.188). However, the benefits inPFS2 were observed in individuals performed PFS1 >6 months (group A) than those of PFS1 ≤6 months (group B) (median PFS2, 4.6 vs. 3.2 months, P=0.038). Multivariate analyses did not reveal any independent prognostic factors for efficacy. Conclusions: The benefits of continuing prior ICIs administration beyond first-line immunotherapy progression might not be obvious in patients with advanced NSCLC, but those first line treatment showed a longer period may receive efficacy benefits.

8.
Med Oncol ; 40(7): 198, 2023 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-37294384

RESUMEN

Invasive mucinous adenocarcinoma (IMA) is a rare variant of adenocarcinoma with unique clinical, radiological, and pathological features, among which KRAS mutation is the most common. However, the differences in the efficacy of immunotherapy between KRAS-positive IMA and invasive non-mucinous adenocarcinoma (INMA) patients remain unclear. Patients with KRAS mutated adenocarcinomas receiving immunotherapy between June 2016 and December 2022 were enrolled. Based on mucin-producing status, the patients were placed into two subgroups: the IMA group and INMA group. Patients with IMA were further classified into two subtypes according to the presence of mucin patterns: pure IMA (≥ 90%) and mixed mucinous/nonmucinous adenocarcinoma (≥ 10% of each histological component). Kaplan-Meier Curves and log-rank tests were used to analyze survival. Cox regression analysis of PFS were used to analyze the independent factors associated with efficacy. Sixty-five advanced adenocarcinoma patients with KRAS mutations received immunotherapy, including 24 patients with IMA and 41 with INMA. The median progression-free survival (PFS) was 7.7 months, whereas the median overall survival (OS) was 24.0 months. Significant difference in PFS could be observed in IMA and INMA (3.5 months vs. 8.9 months; P = 0.047). Patients with pure IMA tended toward prolonger survival in contrast to mixed mucinous/nonmucinous adenocarcinoma in PFS (8.4 months vs. 2.3 months; P = 0.349). The multivariable analysis demonstrated that IMA was an independent risk factor for PFS. In KRAS mutated patients, IMA was associated with poorer PFS after immunotherapy compared with INMA.


Asunto(s)
Adenocarcinoma del Pulmón , Adenocarcinoma Mucinoso , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Adenocarcinoma/genética , Adenocarcinoma/terapia , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/terapia , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/terapia , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/tratamiento farmacológico , Mucinas/genética , Mucinas/metabolismo , Mucinas/uso terapéutico , Mutación , Proteínas Proto-Oncogénicas p21(ras)/genética , Estudios Retrospectivos
9.
J Thorac Dis ; 15(2): 260-269, 2023 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-36910045

RESUMEN

Background: Primary adenosquamous carcinoma (ASC) of the lung is a rare and aggressive disease and limited information is available on the efficacy of immune checkpoint inhibitors (ICIs) for this disease. Here, we evaluated the expression status of programmed death-1 ligand 1 (PD-L1) and efficacy of ICIs in patients with pulmonary ASC. Methods: The efficacy and toxicity of ICIs were examined in 38 patients with previously treated lung ASC from November 2017 to October 2021 in Zhejiang Cancer Hospital (Hangzhou, China). Survival curves were plotted using the Kaplan-Meier method and the Cox proportional hazards model applied for univariate and multivariate analyses. Results: A total of 38 patients with ASC were included in this retrospective study. ICI treatment induced an objective response rate (ORR) of 23.7% and a disease control rate (DCR) of 86.8%. The median progression-free survival (PFS) and median overall survival (OS) were 5.47 and 24.10 months, respectively. Seventeen patients were successfully evaluated for PD-L1 expression status, with 11 (64.7%) identified as PD-L1-positive. ORR and DCR for PD-L1-positive patients were 36.4% (4/11) and 100% (11/11) and the corresponding values for PD-L1-negative patients were 0 (0/6) and 50% (3/6), respectively. The median PFS of PD-L1-positive and PD-L1-negative patient groups was 5.00 and 1.90 months (P=0.166) while the median OS was 11.30 months and not reached, respectively (P=0.966). The incidence rate of immune-related adverse events (irAEs) was 52.6%, with 13.2% grade 3-4 irAEs. The most common irAEs were malaise and pneumonitis. One patient died of pneumonitis during the study. Conclusions: ICIs show considerable potential as a treatment option for lung ASC. PFS and OS rates are similar for PD-L1-positive and PD-L1-negative patients. Further large-scale studies are required to establish the relationship between PD-L1 expression and response to ICIs in ASC.

10.
Transl Cancer Res ; 12(3): 550-557, 2023 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-37033336

RESUMEN

Background: Immune checkpoint inhibitors (ICIs) combined with antiangiogenic therapy have shown promising antitumor activity against a range of advanced cancers. However, evidence is lacking as to whether this combination therapy could benefit thymic epithelial tumors (TETs). We aimed to explore the efficacy and safety of this combination therapy in advanced TETs. Methods: Ten patients with pathologically proven advanced TETs who received ICIs combined with an antiangiogenic agent from 2020 to 2022 at Zhejiang Cancer Hospital were included in the study. The Kaplan-Meier method was used to compare the treatment efficacy and survival outcomes. Results: Of the cohort of ten patients who received immunotherapy combined with antiangiogenic targeting drugs, two patients achieved a partial response (PR) with an objective response rate of 20% and seven patients achieved stable disease (SD) with a disease control rate (DCR) of 90%. The median progression-free survival (PFS) was 6.7 months [95% confidence interval (CI): 3.35-8.515] and the median overall survival (OS) was 45.6 months (95% CI: 3.265-88.001). Grade 3 treatment-related adverse events (TRAEs) were only detected in one patient. No grade 4 or above TRAEs were observed. Conclusions: ICIs in combination with antiangiogenic targeted drugs may be a promising treatment for advanced TETs.

11.
Cancer Med ; 12(5): 5630-5638, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36380563

RESUMEN

BACKGROUND: Few large-scale studies have been published using real-world data related to overall survival (OS) improvements in advanced epidermal growth factor receptor (EGFR)-mutant lung cancer patients; therefore, little is known regarding the characteristics of patients who could benefit most from EGFR-tyrosine kinase inhibitors (TKIs). Our study aimed to assess whether EGFR-TKI treatment confers survival benefits among advanced non-small-cell lung cancer (NSCLC) patients harboring EGFR mutations in the Chinese population. PATIENTS AND METHODS: A total of 6451 advanced NSCLC patients were diagnosed between January 1, 2013 and June 30, 2019 in Zhejiang Cancer Hospital. Ultimately, 2864 patients with a confirmed EGFR mutation genotype were enrolled in our study. OS was measured from the time of diagnosis of advanced NSCLC until death or last follow-up. RESULTS: Median follow-up for OS of advanced EGFR-mutant NSCLC patients was 28.33 months in our study. Patients who received EGFR-TKIs demonstrated better survival compared to those without EGFR-TKI treatment (mOS: 29.77 vs. 22.97 months, p < 0.0001). A total of 451 patients switched to third-generation EGFR-TKI treatment and obtained a significantly better survival than those who adopted first-line third-generation EGFR-TKIs or those who did not receive third-generation EGFR-TKIs after disease progression with first- or second-generation EGFR-TKI treatment (mOS: 38.0 vs. 32.5 vs. 28.3 months, p < 0.0001). As for EGFR genotypes, patients with exon 19 deletion showed better OS, followed by those with L858R mutation (32.4 vs. 24.83 months, p = 0.0013). NGS versus PCR testing showed no statistical differences with respect to survival outcomes (mOS: 27.5 vs. 27.47 months, p = 0.6745). CONCLUSION: Advanced EGFR-mutant patients treated with EGFR-TKIs obtained absolute superior survival in the Chinese population.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Inhibidores de Proteínas Quinasas/uso terapéutico , Supervivencia sin Enfermedad , Mutación , Receptores ErbB/genética , Estudios Retrospectivos
12.
Open Med (Wars) ; 18(1): 20230653, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36915627

RESUMEN

The efficacy of immune checkpoint inhibitors (ICIs) on KRAS-mutant advanced non-small cell lung cancer (NSCLC) remains controversial. This retrospective study compared the effects of ICIs treatment and chemotherapy on the prognosis of patients with KRAS-mutant advanced NSCLC and different mutant subtypes in the real world. The study included 95 patients with KRAS-mutant advanced NSCLC. Patients treated with first-line ICIs plus platinum-containing chemotherapy had better progression-free survival (PFS) (7.4 vs 4.5 months, P = 0.035) and overall survival (OS) (24.1 vs 13.2 months, P = 0.007) than those receiving platinum-containing chemotherapy alone, and second-line ICI monotherapy was associated with better PFS (4.8 vs 3.0 months, P = 0.043) and OS (18.0 vs 13.8 months, P = 0.013) than chemotherapy monotherapy. There was no significant difference in PFS (5.267 vs 6.734 months, P = 0.969) and OS (19.933 vs 20.933 months, P = 0.808) between patients with KRAS-mutant and KRAS-wild-type NSCLC treated with ICIs or between KRAS G12C and KRAS non-G12C patients (PFS: 8.1 vs 4.8 months, P = 0.307; OS: 21.3 vs 21.8 months, P = 0.434). In summary, patients with advanced NSCLC with KRAS mutations can benefit from ICIs, but no difference between KRAS mutant subtypes was observed.

13.
Ann Palliat Med ; 11(5): 1624-1634, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35016520

RESUMEN

BACKGROUND: This study aimed to explore the efficacy of different epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in lung adenocarcinoma (AC) patients harboring uncommon EGFR mutations. METHODS: Between January 1st, 2013 and October 1st, 2019, 2,680 EGFR mutation-positive patients with confirmed stage IIIB/IV lung AC were enrolled from Zhejiang Cancer Hospital. Uncommon EGFR mutations were detected in 132 patients using next-generation-sequencing. Clinicopathological features between patients with uncommon EGFR mutations and common EGFR mutations were evaluated by the chi-square test. The clinical outcomes of patients with uncommon EGFR mutations were analyzed by the Kaplan-Meier method. RESULTS: Of 132 AC patients with uncommon EGFR mutations, 115 received EGFR-TKIs. Second-generation EGFR-TKIs were associated with longer progression-free survival (PFS) (P=0.116) and overall survival (OS) (P=0.005) than first or third-generation EGFR-TKIs. We also found that patients with compound mutations and double uncommon EGFR mutations had longer PFS (P=0.725) and OS (P=0.741) than those with single uncommon EGFR mutation, although the difference was not significant. In addition, third-generation EGFR-TKIs were more effective than the other two agents in patients with primary T790M mutation regarding PFS (P=0.150) and OS (P=0.033), although the difference in PFS was not significant. CONCLUSIONS: Patients with uncommon EGFR mutations treated with second-generation EGFR-TKIs showed better PFS and OS. EGFR-TKIs were more effective in patients with compound mutations or double uncommon mutations.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Mutación , Inhibidores de Proteínas Quinasas/uso terapéutico
14.
Med Oncol ; 40(1): 34, 2022 Dec 02.
Artículo en Inglés | MEDLINE | ID: mdl-36460861

RESUMEN

EGFR-tyrosine kinase inhibitors (TKIs) show efficacy against lung cancer, and afatinib has been used as a standard therapy for patients with non-small cell lung cancer (NSCLC) with EGFR rare mutations such as S768I, G719X, and L861Q. However, the efficacy of EGFR-TKIs against NSCLC with EGFR rare mutations of exon 18 E709X has been less studied. The present study aimed to analyze the efficacy and safety of EGFR-TKIs in NSCLC patients with rare mutations. Our study enrolled 15 NSCLC patients with exon 18 E709X mutation who were admitted to Zhejiang Cancer Hospital. The objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs) were analyzed. The ORR of the entire cohort of patients was 33.3%. The PFS of all patients with exon 18 E709X mutations was 10.9 months. The OS was not reached. The PFS of patients with exon 18 E709-T710delinsD and E709A/G/K mutations showed no significant difference (5.3 vs. 13.5 months, P = 0.238). A significant difference in OS was observed between patients with exon 18 E709-T710delinsD mutation and those with E709A/G/K mutation (12.2 months vs. not reached, P = 0.029). No significant difference in efficacy was observed between second- and third-generation TKIs for NSCLC patients with exon 18 E709X mutations (PFS: 13.5 vs. 10.9 months, P = 0.774; OS: 17.1 months vs. not reached, P = 0.072). New treatment-related adverse events were not observed. NSCLC patients with exon 18 E709X mutations may benefit from treatment with second- or third-generation EGFR-TKIs.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Exones/genética , Inhibidores de Proteínas Quinasas/uso terapéutico , Mutación , Receptores ErbB/genética
15.
Curr Oncol ; 29(12): 9452-9460, 2022 12 02.
Artículo en Inglés | MEDLINE | ID: mdl-36547157

RESUMEN

BACKGROUND: B3 type thymoma is defined as a well-differentiated thymic carcinoma and is similar to a thymic carcinoma. However, the differences between them are not well defined. In addition, the data to compare the efficacy and safety of platinum-based chemotherapy as first-line therapy between B3 thymoma and thymic carcinoma are lacking. METHODS: The efficacy and safety of platinum-based chemotherapy as first-line therapy was retrospectively compared between a group of 36 patients with type B3 thymoma and a group of 127 patients with thymic carcinoma treated between January 2009 and March 2022 at the Zhejiang Cancer Hospital. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events were analyzed. RESULTS: The ORRs for B3 thymoma and thymic carcinoma were 36.1% and 28.3%, respectively (p = 0.370). Among all patients, the difference in PFS between B3 thymoma and thymic carcinoma was not significant (11.3 vs. 10.1 months, p = 0.118). The squamous carcinoma subgroup did not exhibit any differences in PFS compared to B3 thymoma (11.7 vs. 11.3 months, p = 0.161). The result for the non-squamous carcinoma subgroup was similar (6.5 vs. 11.3 months, p = 0.128). Furthermore, the OS values for B3 thymoma and thymic carcinoma were not significantly different (58.3 vs. 35.1 months, p = 0.067). However, there were differences in OS between B3 thymoma and non-squamous carcinoma (58.3 vs. 30.6 months, p = 0.031). CONCLUSIONS: B3 thymoma and especially squamous carcinoma patients may be treated using a similar therapy scheme as that utilized for thymic carcinoma.


Asunto(s)
Carcinoma de Células Escamosas , Timoma , Neoplasias del Timo , Humanos , Timoma/tratamiento farmacológico , Timoma/patología , Platino (Metal)/uso terapéutico , Estudios Retrospectivos , Neoplasias del Timo/tratamiento farmacológico , Neoplasias del Timo/patología , Carcinoma de Células Escamosas/patología
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