Real-world study on the efficacy and prognostic predictive biomarker of patients with metastatic non-small cell lung cancer treated with programmed death-1/programmed death ligand 1 inhibitors / 中华肿瘤杂志

Objective: To describe the actual efficacy of programmed death-1 (PD-1)/ programmed-death ligand 1 (PD-L1) inhibitors in patients with metastatic non-small cell lung cancer (NSCLC) and explore potential prognostic predictive biomarkers. Methods: Patients with metastatic NSCLC who were treated with PD-1/PD-L1 inhibitors at Cancer Hospital, Chinese Academy of Medical Sciences from January 2016 to December 2019, either as monotherapy or in combination with other agents, were consecutively enrolled into this study. We retrospectively collected the data of demographics, clinical information and pathologic assessment to evaluate the therapeutic efficacy and conduct the survival analysis. Major endpoint of our study is progression-free survival (PFS). Secondary endpoints include objective response rate (ORR), disease control rate (DCR) and overall survival (OS). Results: The ORR of 174 patients who underwent PD-1/PD-L1 inhibitor was 28.7%, and the DCR was 79.3%. Immune-related adverse events (irAEs) occurred in 23 patients (13.2%). Brain metastasis, line of treatment, and treatment patterns were associated with the ORR of metastatic NSCLC patients who underwent immunotherapy (P<0.05). After a median follow-up duration of 18.8 months, the median PFS was 10.5 months (ranged from 1.5 to 40.8 months) while the median OS was not reached. The 2-year survival rate was estimated to be 63.0%. The pathologic type was related with the PFS of metastatic NSCLC patients who underwent immunotherapy (P=0.028). Sex, age, brain metastasis and autoimmune diseases were associated with OS (P<0.05). Analysis of the receptor characteristic curve (ROC) of neutrophil/lymphocyte ratio (NLR) predicting ORR of immunotherapy in metastatic NSCLC showed that the areas under the curve of NLR before immunotherapy (NLR(C0)), NLR after one cycle of immunotherapy (NLR(C1)) and ΔNLR were 0.600, 0.706 and 0.628, respectively. Multivariate logistic regression analysis showed that NLR(C1) was an independent factor of the ORR of metastatic NSCLC patients who underwent immunotherapy (OR=0.161, 95% CI: 0.062-0.422), and the efficacy of combination therapy was better than that of single agent (OR=0.395, 95% CI: 0.174-0.896). The immunotherapy efficacy in patients without brain metastasis was better than those with metastasis (OR=0.291, 95% CI: 0.095-0.887). Multivariate Cox regression analysis showed that NLR(C1) was an independent influencing factor of PFS of metastatic NSCLC patients after immunotherapy (HR=0.480, 95% CI: 0.303-0.759). Sex (HR=0.399, 95% CI: 0.161-0.991, P=0.048), age (HR=0.356, 95% CI: 0.170-0.745, P=0.006) were independent influencing factors of OS of metastatic NSCLC patients after immunotherapy. Conclusions: PD-1/PD-L1 inhibitors are proved to be efficacious and have tolerable toxicities for patients with metastatic NSCLC. Patients at advanced age could still benefit from immunotherapy. Brain metastasis is related to compromised response. Earlier application of immunotherapy in combination with other modalities enhances the efficacy without elevating risk of irAEs. NLR(C1) is an early predictor of clinical outcome. The OS of patients younger than 75 years may be improved when treated with immunotherapy.

Efficacy of erlotinib after the failure of gefitinib in patients with metastasis of non-small cell lung cancer with unknown EGFR mutation status / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of erlotinib in patients with metastasis of non-small cell lung cancer who had benefits from initial gefitinib treatment but finally demonstrated resistance, especially in those of unknown EGFR mutation status, and to compare the efficacy of erlotinib between patients who received erlotinib immediately after gefitinib failure and those who received chemotherapy before erlotinib.</p><p><b>METHODS</b>Forty Chinese patients who had been treated with erlotinib (150 mg daily) after gefitinib (250 mg daily) failure were evaluated retrospectively. All of these patients had achieved gefitinib treatment for at least three months with response of partial remission or stable disease. Among them, 16 patients shifted to erlotinib immediately after progression (Group G-E), and the other 24 patients inserted chemotherapy between gefitinib and erlotinib (Group G-C-E).</p><p><b>RESULTS</b>In the whole group, the disease control rate (DCR) of erlotinib was 52.5% (21/40) while the objective response rate (RR) was only 10.0% (4/40). The RR of the group G-E was 6.2% and the group G-C-E was 12.5%, and the DCR was 56.2% and 50.0% in the two groups, respectively, both without significant differences (P = 0.638 and P = 0.755). There was no correlation between the efficacy of erlotinib and that of initial gefitinib in both group G-E and group G-C-E (P = 0.365 and P = 0.658). The median progression-free survival (PFS) and overall survival (OS) for the erlotinib treatment were 3.0 and 12.0 months in the 40 patients. Statistically no significant difference was observed in PFS (4 months in the group G-E and 2 months in the group G-C-E, P = 0.768) and OS (12 months in both Groups, P = 0.510).</p><p><b>CONCLUSIONS</b>Erlotinib can be considered either immediately after gefitinib failure or following the insertion of chemotherapy after gefitinib failure in progressive non-small cell lung cancer patients who initially benefited from gefitinib.</p>

Factors affecting the sensitivity of EGFR-TKI treatment in advanced non-small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the clinical factors affecting the sensitivity of EGFR-TKI treatment in advanced non-small cell lung cancer.</p><p><b>METHODS</b>Clinical data were retrospective analyzed to determine the clinical factors affecting the outcome of 166 patients with advanced non-small cell lung cancer who received EGFR-TKI treatment in our hospttal from January of 2005 to December of 2006.</p><p><b>RESULTS</b>One hundred and nineteen patients benefited from EGFR-TKI treatment in the total of 166 patients and the disease control rate was 71.7%. Among the factors analyzed, sex, age, smoking, pathological type, brain and bone metastasis or not when EGFR-TKI was used, the time using EGFR-TKI and the level of LDH at the time of diagnosis had no significant effect on the clinical benefit rate. Among the 126 patients with serum CEA assayed at diagnosis, 84 cases had a higher serum CEA level. Compared with the patients with normal serum CEA level, the patients with a higher serum CEA level benefited more easily from EGFR-TKI therapy, with a disease control rate of 79.8% and 59.5%, respectively (P = 0.016). Among the patients who got benefits from EGFR-TKI treatment, smoking and the CEA level at diagnosis had effects on the duration of progression-free survival. The progression free survivals were 9.57 ± 6.75 months in non-smokers, 4.86 ± 3.44 months in light-smokers and 5.25 ± 4.34 months in heavy-smokers (P = 0.007). The progression free survival was 9.45 ± 7.48 months in the group with a higher serum CEA level and 6.52 ± 4.46 months in the group with normal serum CEA level (P = 0.036).</p><p><b>CONCLUSIONS</b>In patients with advanced non-small cell lung cancer, EGFR-TKIs treatment is safe and effective. The patients with high CEA level are prone to benefit from it.</p>

Association of serum EGFR protein concentration with the efficacy of Gefitinib in the treatment of advanced non-small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze the association between the EGFR protein level and the EGFR gene mutation status in advanced non-small cell lung cancer (NSCLC), and to explore whether the EGFR protein level is related to the efficacy and survival of the EGFR-TKI drug Gifitinib-treated patients with advanced NSCLC.</p><p><b>METHODS</b>Ninety-nine cases were enrolled in this study. Pathological tissue specimens and paired peripheral blood samples were collected. Exons 19 and 21 of the EGFR gene mutation were detected by direct sequencing. The concentration of plasma EGFR protein was detected by ELISA. Univariate and multivariate statistical analyses of the efficacy and survival were performed using SPSS 13.0 software.</p><p><b>RESULTS</b>The response rate (RR) and clinical benefit rate (CBR) of Gefitinib-treated patients were 51.5% and 79.8%, respectively. There were 35 (35.4%) with positive EGFR gene mutation of the 99 samples. The concentration limit of EGFR protein was 55.42 µg/L. The RR and CBR of patients with EGFR gene mutation was significantly higher than those without mutation (65.7% vs. 43.8%, P = 0.037; 94.3% vs. 71.9%, P = 0.008). The median PFS was prolonged (23 months vs. 10 months, P = 0.014). The CBR of patients with high EGFR protein expression (concentration ≥ 55.42 µg/L) was significantly higher than those with low expression (90.0% vs 64.1%, P = 0.004), and the median PFS was prolonged (21 months vs. 8 months, P = 0.016). EGFR protein level was an independent factor affecting the EGFR gene mutation status. The Correlation between EGFR gene mutation status and EGFR protein level was positive.</p><p><b>CONCLUSIONS</b>Gefitinib is effective in the treatment of advanced NSCLC patients with EGFR gene mutation and high EGFR protein expression. EGFR protein level in peripheral blood may be a molecular biomarker in prediction of efficacy and survival of the Gefitinib treatment in patients with advanced NSCLC.</p>

Multicenter phase II clinical trial of arsenic trioxide injection in the treatment of primary hepatocarcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the effect and adverse effects of arsenic trioxide (As2O3) in the treatment of primary hepatocarcinoma patients, and conduct the pharmacokinetics study.</p><p><b>METHODS</b>A total of one hundred and eleven advanced primary hepatocarcinoma patients in five centers were treated with As2O3 injection 7 - 8 mg/m(2) i.v. qd for 14 days and was repeated after 7 - 14 days. Evaluation of the clinical response and adverse effects was conducted after two cycles of treatment. The patient who had reached partial PR and SD was treated continuously until disease progression or intolerance.</p><p><b>RESULTS</b>Among the 102 patients evaluable for clinical efficacy analysis, there were 7 PR, 71 SD and 24 PD, the response rate was 6.9% and the clinical benefit rate was 76.5%. The quality of life was improved in 22.5% of patients. The pain relief rate was 71.7%, time to progress (TTP) was 97 days, and the median survival time (MST) was 195 days. The major adverse effects were reversible WHO I-II grade gastrointestinal reactions and bone marrow suppression. The results of pharmacokinetic study showed that the distribution and elimination characteristics in vivo was found to be a two-compartment model. The plasma elimination half-life was (23.94 ± 18.39) h.</p><p><b>CONCLUSIONS</b>As2O3 is effective in the management of primary hepatocarcinoma, with a significant analgesic effect. To some extent, it can extend TTP and MST in advanced liver cancer patients, while the treatment is well tolerated in the majority of patients.</p>

Long-term outcomes of gemcitabine and cisplatin in patients with recurrent or metastatic esophageal squamous cell carcinoma: a phase II trial / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Esophageal cancer is the sixth most common cause of cancer-related death worldwide. Prior studies had demonstrated potential synergistic antitumor activity of gemcitabine in combination with cisplatin. Therefore, we studied the efficacy and tolerability of such combination for esophageal cancer.</p><p><b>METHODS</b>Between October 2003 and October 2006, thirty-eight patients with metastatic or recurrent advanced squamous cell carcinoma of the esophagus were enrolled. The median number of treatment cycles per patient was 4 (range 1 - 7). Gemcitabine was given at 1000 mg/m(2) over 30 minutes on days 1, 8 and cisplatin 40 mg/m2 was given on days 1, 2 in an every 21-day cycle.</p><p><b>RESULTS</b>The median follow-up for all 38 patients was 76 months (range 11 - 88 months). The overall response rate was 42.1% (95%CI, 25.5% - 56.5%). Median progression-free survival and median survival for all patients were 4.1 months (95%CI, 3.0 - 5.7 months) and 10 months (95%CI, 7 - 12 months), respectively. Patients with a response had significantly longer median survival compared with the patients without a response (11 months vs. 7.5 months, P = 0.0069). Overall survival at 1 year was 36.8%, at 2 years was 10.5%, and at 5 years was 5.3%. The most common grade 3 - 4 toxicity for all patients was leucopenia (44.7%).</p><p><b>CONCLUSIONS</b>This cisplatin-gemcitabine regimen was manageable and had significant efficacy in patients with esophageal squamous cell carcinoma. Patients with a response had improved survival time. Furthermore, a small number of the patients with metastatic esophageal cancer were still alive in 5 years with this regimen.</p>