Response characteristics of tislelizumab combined with chemotherapy in first-line treatment of locally advanced or metastatic non-squamous non-small cell lung cancer / 中华肿瘤杂志

Objective: To investigate the response characteristics of patients with locally advanced/metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) treated with tislelizumab in combination with chemotherapy in the first line. Methods: Patients with nsq-NSCLC who achieved complete or partial remission after treatment with tislelizumab in combination with chemotherapy or chemotherapy alone in the RATIONALE 304 study, as assessed by an independent review board, were selected to analyze the response characteristics and safety profile of the responders. Time to response (TTR) was defined as the time from randomization to the achievement of first objective response. Depth of response (DpR) was defined as the maximum percentage of tumor shrinkage compared with the sum of the baseline target lesion length diameters. Results: As of January 23, 2020, 128 patients treated with tislelizumab in combination with chemotherapy achieved objective tumor response (responders), representing 57.4%(128/223) of the intention-to-treat population, with a TTR of 5.1 to 33.3 weeks and a median TTR of 7.9 weeks. Of the responders (128), 50.8%(65) achieved first remission at the first efficacy assessment (week 6), 31.3%(40) at the second efficacy assessment (week 12), and 18.0%(23) at the third and subsequent tumor assessments. The percentages of responders who achieved a depth of tumor response of 30% to <50%, 50% to <70% and 70% to 100% were 45.3%(58/128), 28.1%(36/128) and 26.6%(34/128), respectively, with median progression-free survival (PFS) of 9.0 months (95% CI: 7.7 to 9.9 months), 11.5 months (95% CI: 7.7 months to not reached) and not reached (95% CI: 11.8 months to not estimable), respectively. Tislelizumab plus chemotherapy were generally well tolerated in responders with similar safety profile to the overall safety population. Conclusion: Among responders to tislelizumab in combination with chemotherapy for nsq-NSCLC, 82.0%(105/128) achieves response within the first two tumor assessments (12 weeks) and 18.0%(23/128) achieves response at later (18 to 33 weeks) assessments, and there is a trend toward prolonged PFS in responders with deeper tumor response.

EGFR Mutation Is Associated with Short Progression-Free Survival in Patients with Stage III Non-squamous Cell Lung Cancer Treated with Concurrent Chemoradiotherapy / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study was conducted to evaluate the relationship between epidermal growth factor receptor (EGFR) mutation and clinical outcomes in patients with stage III non-squamous cell lung cancer treated with definitive concurrent chemoradiotherapy (CCRT). MATERIALS AND METHODS: From January 2008 to December 2013, the medical records of 197 patients with stage III non- squamous non-small cell lung cancer treated with definitive CCRT were analyzed to determine progression-free survival (PFS) and overall survival (OS) according to EGFR mutation status. RESULTS: Among 197 eligible patients, 81 patients were EGFR wild type, 36 patients had an EGFR mutation (exon 19 Del, n=18; L858R, n=9, uncommon [G719X, L868, T790M], n=9), and 80 patients had unknown EGFR status. The median age was 59 years (range, 28 to 80 years) and 136 patients (69.0%) were male. The median follow-up duration was 66.5 months (range, 1.9 to 114.5 months). One hundred sixty-four patients (83.2%) experienced disease progression. Median PFS was 8.9 months for the EGFR mutation group, 11.8 months for EGFR wild type, and 10.5 months for the unknown EGFR group (p=0.013 and p=0.042, respectively). The most common site of metastasis in the EGFR mutant group was the brain. However, there was no significant difference in OS among the three groups (34.6 months for EGFR mutant group vs. 31.9 months for EGFR wild type vs. 22.6 months for EGFR unknown group; p=0.792 and p=0.284). A total of 29 patients (80.6%) with EGFR mutation were treated with EGFR tyrosine kinase inhibitor (gefitinib, n=24; erlotinib, n=3; afatinib, n=2) upon progression. CONCLUSION: EGFR mutation is associatedwith short PFS and the brain is the most common site of distant metastasis in patients with stage III non- squamous cell lung cancer treated with CCRT.

Clinicial efficacy and prognosis of bevacizumab combined with chemotherapy in retreated advanced non-squamous non-small cell lung cancer / 中国肿瘤临床

Objective:To investigate the efficacy and safety of bevacizumab combined with chemotherapy in patients with retreated advanced non-squamous non-small cell lung cancer (NSNSCLC) and analyze its prognostic factors. Methods:Forty-one patients with previously treated advanced NSNSCLC in Beijing Chest Hospital from February 2013 to June 2017 were recruited. Clinical data of the patients were retrospectively analyzed. There were 38 cases of adenocarcinoma and 3 cases of other pathological types. Bevacizumab combined with chemotherapy served as second-line treatment for 19 patients, and it served as beyond second-line therapy for 22 pa-tients. Eighteen patients harbored epidermal growth factor receptor (EGFR) gene mutations, while the other 23 patients harbored wild-type EGFR gene. The efficacy and safety of bevacizumab combined with chemotherapy were evaluated. To evaluate the prognos-tic factors, single and multiple factor analyses were conducted. Results:All patients received bevacizumab combined with chemothera-py and could be evaluated for response. The mean number of cycles of chemotherapy and chemotherapy combined with bevacizumab were 3.1 and 5.0, respectively. The objective response rate (ORR) of all recruited patients was 12.2％. The disease control rate (DCR) was 82.9％. Regarding the effect of second-line and beyond second-line therapy in patients, data were similar. The ORRs were 10.5％and 13.6％, respectively (P=0.572), and DCRs were 89.5％and 77.3％, respectively, without significantly statistical difference (P=0.271). The median progression-free survival (PFS) and overall survival (OS) were 4.6 months [95％confidence interval (CI) 3.619-5.581] and 11.9 months (95％CI 9.797-14.003), respectively. In the single factor analysis, patients with EGFR mutations, those who received>4 cy-cles of bevacizumab administration, and women had longer OS (χ2=19.673, P=0.000;χ2=6.820, P=0.009;andχ2=6.374, P=0.012;respec-tively). The Cox regression analysis showed that EGFR mutation status and number of cycles of bevacizumab administration were inde-pendent prognostic factors [hazard ratio (HR)=0.129, P=0.001 and HR=0.336, P=0.012;respectively]. The common adverse reactions in-clude bone marrow suppression, bleeding, hypertension, and proteinuria. Most of them were grade 1-2. Conclusions:Bevacizumab combined with chemotherapy provides good efficacy and controllable safety in patients with retreated advanced NSNSCLC. Patients with EGFR mutations and>4 cycles of bevacizumab administration have superior prognosis.

Clinical research on apatinib combined with Xiaoyan decoction for the treatment of non-squamous non-small cell lung cancer / 中国肿瘤临床

Objective:To determine the effect of apatinib combined with Xiaoyan decoction for the treatment of non-squamous non-small cell lung cancer. Methods:Thirty-eight patients with non-squamous non-small cell lung cancer were randomly categorized into apatinib group (group A, 18 cases) and apatinib combined with Xiaoyan decoction group (group B, 20 cases). All patients did not under-go surgical treatment, radiotherapy, or chemotherapy during the study. Results:The median progression free survival (mPFS) of ad-vanced non-squamous non-small cell lung cancer patients reached up to 3 months. The mPFS, objective response rate, and disease control rate of the apatinib combined with Xiaoyan decoction group showed no significant difference and statistical significance (P>0.05). The apatinib combined with Xiaoyan decoction group was superior to the apatinib group with regard to alleviating clinical symp-toms and adverse reactions (P<0.05). Conclusion:Xiaoyan decoction combined with apatinib can improve the clinical symptoms of pa-tients and reduce the incidence of adverse reactions in the treatment of advanced non-squamous non-small cell lung cancer.