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Objective:To investigate the progression pattern of acquired resistance to osimertinib and the treatment method as well as the therapeutic effect of salvage therapy in advanced lung cancer patients with epidermal growth factor receptor (EGFR) sensitive mutation or T790M mutation after the treatment of tyrosine-kinase inhibitor (TKI).Methods:The data of 145 patients with advanced lung cancer treated with osimertinib in Jiangsu Cancer Hospital between April 2017 (the approval time of osimertinib in China) and May 2019 were collected. At the last follow-up (December 2019), a total of 87 (60.0%) patients had acquired resistance to osimertinib, 61 (70.1%) of whom received salvage treatment; for patients with dramatic progression after resistance, chemotherapy was mainly given in the salvage therapy; for patients with gradual or local progression after resistance, the continuing targeted drug therapy and the local therapy were given. Imaging evaluation and Kaplan-Meier method were used to analyze the progression pattern of acquired resistance to osimertinib and the survival status, and to compare the salvage treatment results among subgroups.Results:The median follow-up time of 61 patients receiving salvage therapy was 11 months (4-32 months), among which 58 (95.1%) patients again had resistance to osimertinib, and 24 (39.3%) patients died of lung cancer. The median progression-free survival (PFS) time and overall survival (OS) time for the whole cohort was 2.5 months (95% CI 2.1-3.0 months) and 19.0 months (95% CI 13.7-26.3 months), respectively. The 1-year and 2-year OS rate was 72.1% and 41.7%, respectively. Among 61 patients receiving salvage therapy, 8 (13.1%) , 30 (49.2%) and 23 (37.7%) cases had dramatic progression, gradual progression and local progression, respectively; when given timely and proper salvage treatment, there were no statistically differences in PFS and OS of the patients in the above three subgroups (all P>0.05). There were no statistically differences in PFS and OS between patients receiving local therapy (24 cases) and patients not receiving local therapy (37 cases) after the progression occurred (all P>0.05). Among 58 patients with resistance to osimertinib again after the salvage therapy, 6 patients with gradual or local progression had more than 6-mouth PFS after the salvage therapy. Conclusions:Dramatic, gradual and local progression are the main patterns in patients with acquired resistance to osimertinib. The therapeutic efficacy of salvage therapy still shows some disappointing results.
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Objective:To investigate the type and severity of skin adverse reactions induced by afatinib in the treatment of lung cancer, and to analyze their correlation with anti-lung cancer efficacy.Methods:A case-case-control study was conducted on lung cancer patients treated with afatinib in ZhongDa Hospital, Southeast University from December 2016 to January 2018. The type and severity of skin adverse reactions were evaluated in 76 patients with lung cancer based on the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.0, and these patients were divided into 3 groups according to the severity of skin lesions, including grade-0, -1, and -2/3 groups. The patients underwent chest computed tomography (CT) examination every 3 months, and the tumor response to afatinib was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) . Anti-lung cancer efficacy of afatinib was compared among the patients with different grades of skin lesions by using the Kruskal-wallis H rank sum test. Results:After treatment with afatinib, 44 of the 76 patients with lung cancer achieved stable condition or partial remission, and 32 experienced disease progression. Skin adverse reactions occurred in 69 patients, and manifested as acneiform lesions in 42 (55.3%) patients, paronychia in 35 (46.1%) , mucosal erosions in 30 (39%) , hair changes in 8 (10.5%) , and hand-foot syndrome in 6 (7.9%) . Improvement was achieved in 3, 7 and 34 cases in the grade-0, -1, and -2/3 groups ( n = 7, 19 and 50 respectively) , respectively. There was a significant difference in the response rate among the 3 groups ( χ2 = 6.117, P = 0.047) , and the response rate was significantly higher in the grade-1 and -2/3 groups than in the grade-0 group (both P < 0.001) , and higher in the grade-2/3 group than in the grade-1 group ( P < 0.001) . Conclusion:The treatment of lung cancer with afatinib can cause various types of skin lesions, such as acneiform lesions, paronychia, mucosal erosions, hair changes and hand-foot syndrome, and the higher the severity of the skin lesions, the more marked the anti-lung cancer efficacy of afatinib.
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Objective: Non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR)-activating mutations have higher response rate and more prolonged survival following treatment with single-agent EGFR tyrosine kinase inhibitor (EGFR-TKI) compared with patients with wild-type EGFR. However, all patients treated with reversible inhibitors develop acquired re-sistance over time. The mechanisms of resistance are complicated. The lack of established therapeutic options for patients after a failed EGFR-TKI treatment poses a great challenge to physicians in managing this group of lung cancer patients. This study evaluates the in-fluence of EGFR-TKI retreatment following chemotherapy after failure of initial EGFR-TKI within at least six months on NSCLC pa-tients. Methods:The data of 27 patients who experienced treatment failure from their initial use of EGFR-TKI within at least 6 months were analyzed. After chemotherapy, the patients were retreated with EGFR-TKI (gefitinib 250 mg qd or erlotinib 150 mg qd), and the tumor progression was observed. The patients were assessed for adverse events and response to therapy. Targeted tumor lesions were as-sessed with CT scan. Results:Of the 27 patients who received EGFR–TKI retreatment, 1 (3.7%) patient was observed in complete re-sponse (CR), 8 (29.6%) patients in partial response (PR), 14 (51.9%) patients in stable disease (SD), and 4 (14.8%) patients in progres-sive disease (PD). The disease control rate (DCR) was 85.2%(95%CI=62%-94%). The median progression-free survival (mPFS) was 6 months (95%CI=1-29). Of the 13 patients who received the same EGFR-TKI, 1 patient in CR, 3 patients in PR, 8 patients in SD, and 2 patients in PD were observed. The DCR was 84.6%, and the mPFS was 5 months. Of the 14 patients who received another EG-FR-TKI, 0 patient in CR, 6 patients in PR, 6 patients in SD, and 2 patients in PD were observed. The DCR was 85.7%, and the mPFS was 9.5 months. Significant difference was found between the 2 groups in progression-free survival but not in response rate or disease control rate. Conclusion:Retreatment of EGFR-TKIs can be considered an option after failure of chemotherapy for patients who were previously controlled by EGFR-TKI treatment.
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<p><b>BACKGROUND</b>Gensing Rg3 is an active component from ginseng. The aim of this study is to observe the clinical anticancer effect of Rg3 in combination with chemotherapy regimen NP (vinorelbine+cisplatin) in advanced non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>Stage III-IV NSCLC patients confirmed by pathology or cytology all received vinorelbine plus cisplatin for at least two cycles, and were randomized into two groups: patients in arm A also received placebo twice a day, while patients in arm B received two tablets of Rg3 twice a day for at least two months. The endpoints of the study were the efficacy, survival and tolerance of patients.</p><p><b>RESULTS</b>From July 2000 to May 2002, 115 patients were enrolled into the trial. The patients' characteristics were well balanced in the two groups. Sex of patients: male, 79; female 36. Types of pathology: adenocarcinoma, 71; squamous cell carcinoma, 29; adenosquamous carcinoma, 8; others, 7. TNM stage: stage III, 45; stage IV, 70. Prior chemotherapy: with, 17; without, 98. Prior radiotherapy: with, 15; without, 100. Prior surgical treatment: with, 23; without, 92. Nine patients discontinued from the trial due to severe adverse effects (5) and other reasons (4), so there were 106 patients evaluable for clinical efficacy. The response rate was 14.5% (8/55) in arm A, and 33.3% (17/51) in arm B (P=0.011). The survival time in arm A was 9.7 months (mean) and 8.0 months (median), and 15.3 months (mean) and 10.0 months (median) in arm B (P=0.0088).</p><p><b>CONCLUSIONS</b>Preliminary results show improvements in response rate and survival time (median and mean) in Rg3 arm compared with placebo arm. It is worthy to confirm the results in further clinical trials.</p>
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<p><b>BACKGROUND</b>Methylenetetrahydrofolate reductase (MTHFR) plays an important role in metabolism of folate and DNA methylation. In vitro, many studies have demonstrated that abnormal methylation of some genes may affect the sensitivity of tumor cells to cytotoxic drugs and agents interfering with DNA synthesis. The aim of this study is to investigate the relationship between genetic polymorphisms of MTHFR C677T or A1298C and the response to platinum-based chemotherapy in non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>A total of 97 patients with NSCLC were analyzed. MTHFR genotypes were detected in all the patients by PCR-RFLP method. All the patients were treated with platinum-based chemotherapy.</p><p><b>RESULTS</b>(1) Out of all the cases, the frequencies of MTHFR C677T C/C, C/T and T/T genotypes were 34.0%, 50.5% and 15.5%, respectively, while the frequencies of MTHFR A1298C A/A, A/C and C/C genotypes were 64.6%, 29.2% and 6.3%, respectively. The overall response rate (complete and partial response) to platinum-based chemotherapy was 39.2%. (2) No significant difference in response rate to chemotherapy was observed according to the MTHFR C677T or A1298C genotypes. However, MTHFR C677T and A1298C polymorphisms showed a synergic effect on chemotherapeutic efficacy, the response rate of patients with MTHFR C677T T allele and A1298C A/A genotype (51.1%) was significantly higher than those with MTHFR C677T C/T and A1298C C allele (12.5%)(P=0.007, OR=7.30, 95% CI: 1.34-52.47).</p><p><b>CONCLUSIONS</b>The results suggest that the synergic effect between MTHFR C677T and A1298C polymorphisms is associated with clinical response to platinum-based chemotherapy. Detection of MTHFR genotypes may indicate the sensitivity of NSCLC patients to platinum-based chemotherapy.</p>