Efficacy of First-line Chemotherapy Affects the Second-Line Setting Response in Patients with Advanced Non-Small Cell Lung Cancer

Background: Chemotherapy is the mainstay of treatment for the majority of patients with advanced nonsmall cell lung cancer (NSCLC) without driver mutations and many receive therapies beyond first-line. Secondline chemotherapy has been disappointing both in terms of response rate and survival and we know relatively little about the prognostic factors. Materials and Methods: One thousand and eight patients with advanced NSCLC who received second-line chemotherapy after progression were reviewed in Shanghai PulmonaryHospital, China, from September 2005 to July 2010. We analyzed the effects of potential prognostic factors on the outcomes of second-line chemotherapy (overall response rate, ORR; progression free survival, PFS; overall survival, OS). Results: The response and progression free survival of first-line chemotherapy affects the ORR, PFS and OS of second-line chemotherapy (ORR: CR/PR 15.4%, SD 10.1%, PD2.3%, p<0.001; PFS: CR/PR 3.80 months, SD 2.77 months, PD 2.03 months, p<0.001; OS: CR/PR 11.60 months, SD 10.33 months, PD 6.57 months, p=0.578, p<0.001, p<0.001, respectively). On multivariate analysis, better response to first-line therapy (CR/PR: HR=0.751, p=0.002; SD: HR=0.781, p=0.021) and progression within 3-6 months (HR=0.626, p<0.001), together with adenocarcinoma (HR=0.815, p=0.017), without liver metastasis (HR=0.541, p=0.001), never-smoker(HR=0.772, p=0.001), and ECOG PS 0-1 (HR=0.745, p=0.021) were predictors for good OS following secondline chemotherapy. Conclusions: Patients who responded to first-line chemotherapy had a better outcome after second-line therapy for advanced NSCLC, and the efficacy of first-line chemotherapy, period of progression, histology, liver metastasis, smoking status and ECOG PS were independent prognostic factors for OS.     

广泛期小细胞肺癌一线化疗肿瘤缓解深度与生存期的相关性

目的:分析广泛期小细胞肺癌一线化疗后肿瘤缓解深度与患者生存期的相关性。方法:回顾性分析符合入组条件的50例初治广泛期小细胞肺癌患者的临床资料。通过Spearman秩相关检验评价广泛期小细胞肺癌化疗后肿瘤缓解深度与生存期的相关性，应用Log-rank检验比较不同肿瘤缓解深度对生存期的影响，应用COX比例回归模型进行多因素分析。结果:Spearman秩相关分析显示肿瘤缓解深度与PFS及OS均呈中等程度相关。不同缓解深度患者的生存期存在统计学差异。体重减少（P＜0.000 1）、缓解深度（P＜0.001）为无进展生存期的独立影响因素；体重减少（P＜0.000 1）、体力状态（P=0.001 2）、缓解深度（P＜0.001）、化疗周期（P=0.000 2）、二线治疗（P=0.006 7）为总生存期的独立预后因素。结论:广泛期小细胞肺癌一线化疗后肿瘤缓解深度对患者生存期有一定的预测价值。     

A prognostic model to identify patients with advanced pancreas adenocarcinoma who could benefit from second-line chemotherapy

AimsThe role of salvage chemotherapy after first-line therapy in advanced pancreatic cancer has not yet been established. We intended to identify prognostic factors for long-term survival of advanced pancreatic adenocarcinoma patients with second-line chemotherapy and to devise a prognostic model of clinical parameters.Patients and methodsWe analysed 90 patients who had received second-line chemotherapy after the failure of first-line therapy in recurrent or metastatic pancreatic adenocarcinoma between August 2003 and December 2008.ResultsThe median age at the time of second-line chemotherapy was 61.9 years (range 39.8–74.9) and the median Eastern Cooperative Oncology Group (ECOG) performance status was 1 (0–2). Median progression-free survival and overall survival for second-line chemotherapy were 2.1 and 4.5 months, respectively, with an overall response rate of 10%. In multivariate analysis, an ECOG performance status of 2 or more, non-responder for first-line chemotherapy and albumin level of <3.5 mg/dl were independent prognostic factors for decreased overall survival for all 90 patients. Overall survival was estimated based on the number of adverse prognostic factors: zero or one (good prognostic group), two (intermediate group) or three (poor prognostic group). The median overall survival for good (n = 50), intermediate (n = 24) and poor (n = 16) prognostic groups was 5.5, 3.3 and 2.1 months, respectively (P < 0.001).ConclusionOur result suggests that second-line chemotherapy may be beneficial for overall survival in patients with ECOG performance status 0–1, albumin level ≥3.5 mg/dl and response to first-line chemotherapy.     

A prognostic model in patients treated for metastatic gastric cancer with second-line chemotherapy

BackgroundThis retrospective study was carried out to evaluate the prognostic significance of clinical factors in patients treated for metastatic gastric cancer with second-line chemotherapy.Patients and methodsWe evaluated the prognostic significance of various clinical factors in 126 patients, who were treated with second-line chemotherapy.ResultsMedian progression-free and overall survival (OS) for second-line chemotherapy were 3.3 and 5.3 months, respectively, with an overall response rate of 11.1%. Multivariate analysis identified three independent prognostic factors: performance status: Eastern Cooperative Oncology Group zero to one [hazard ratio (HR) 2.3, 95% confidence interval (CI) 1.7–5.4], hemoglobin (Hb) level: ≥10 g/dl (HR 2.2, 95% CI 2.1–2.4) and time-to-progression (TTP) under first-line therapy: ≥5 months (HR 0.5, 95% CI 0.3–0.8). From the obtained data, a prognostic index was constructed, dividing the patients into three risk groups: good (n = 40), intermediate (n = 36) and poor risk group (n = 56). The median survival for good, intermediate and poor risk groups were 13.5, 6.0 and 2.9 months, respectively, whereas the 1-year OS rates were 50.2%, 14.2% and 2.6%, respectively (P = 0.00001).ConclusionsWith inadequate data from randomized controlled trials at the moment, our report indicates that second-line chemotherapy is effective and beneficial in patients with good performance status, higher Hb level along with higher TTP under first-line therapy.     

Impact of Response to Prior Chemotherapy in Patients With Advanced Urothelial Carcinoma Receiving Second-Line Therapy: Implications for Trial Design

BackgroundThe prognostic impact of response to prior chemotherapy independent of performance status (PS), hemoglobin (Hb), liver metastasis (LM), and time from prior chemotherapy (TFPC) in the context of second-line therapy for advanced urothelial carcinoma (UC) is unknown.MethodsSix phase II trials evaluating second-line therapy (n = 504) were pooled. Patients who received prior therapy for metastatic disease were eligible for analysis if Hb, LM, PS, and TFPC were available. Response by Response Evaluation Criteria in Solid Tumors 1.0 to first-line therapy was recorded. Progression-free survival (PFS) and overall survival (OS) were calculated from the date of registration using the Kaplan–Meier method.ResultsA total of 275 patients were evaluable for analysis. Patients received gemcitabine-paclitaxel, cyclophosphamide-paclitaxel, pazopanib, docetaxel plus vandetanib/placebo, or vinflunine (2 trials). Those with prior response (n = 111) had a median OS of 8.0 months (95% confidence interval [CI], 6.8-9.4), compared with 5.9 months (95% CI, 5.0-6.6) for those without prior response (n = 164). Those with prior response had a median PFS of 3.0 months (95% CI, 2.6-4.0) compared with 2.6 months (95% CI, 2.0-2.8) in patients without response. Multivariable analysis did not reveal a significant independent impact of prior response on PFS and OS.ConclusionsBest prior response in patients receiving prior chemotherapy for metastatic disease did not confer an independent prognostic impact with second-line therapy for advanced UC. Given that the setting of prior chemotherapy (metastatic or perioperative) has not appeared significant in a prior study, patients who received prior chemotherapy in perioperative or metastatic settings may be enrolled in the same second-line trial stratified for PS, Hb, LM, and TFPC.     

诱导化疗联合放疗在早期结外NK/T细胞淋巴瘤的预后分析

目的 分析早期结外NK/T细胞淋巴瘤(ENKTCL)使用诱导化疗联合放疗的疗效及预后因素。方法 2003—2021年间贵州医科大学附属肿瘤医院收治287例早期ENKTCL患者,接受诱导化疗联合放疗的综合治疗,分析早期NKTCL的临床预后相关因素。Kaplan-Meier计算总生存(OS)、无进展生存(PFS)及log-rank法检验和单因素分析,Cox模型多因素分析。结果 全组5年OS、PFS分别为72.8%、68.9%;基于改良的Nomogram风险指数(NRI)预后模型分为低危组(0分)、中低危组(1分)、中高危组(2分)、高危组(3分)和极高危组(≥4分)的5年OS分别为95.6%、76.3%、69.5%、61.0%和23.3%(P<0.001),5年PFS分别为93,2%、69.8%、64.6%、60.2%和23.3%(P<0.001)。放疗剂量≥50Gy和<50Gy组5年OS分别为73.8%和65.9%(P=0.123),5年PFS分别为72.8%和45.3%(P=0.001)。诱导化疗近期疗效为CR、PR、SD、PD的5年OS分别为85.4%、74.0%、61.8%、28.5%(P<0.001),5年PFS分别为83.7%、66.8%、65.7%、27.4%(P<0.001)。单因素分析显示Ⅱ期、ECOG≥2分、超腔、放疗剂量<50Gy、诱导化疗近期疗效为5年OS及PFS的预后不良因素(均P<0.05),多因素分析显示超腔、ECOG≥2分、Ⅱ期为OS预后不良因素(均P<0.05),而超腔、ECOG≥2分为PFS的预后不良因素(均P<0.05)。结论 早期结外NK/T细胞淋巴瘤采用以诱导化疗联合足量放疗能取得较好疗效;对诱导化疗近期疗效能够达到完全缓解预后良好。     

索拉非尼治疗进展期肝细胞癌的疗效及预后因素分析

  目的  评价索拉非尼治疗进展期肝细胞癌（HCC）的疗效及分析其预后影响因素。  方法  前瞻性分析2007年8月至2009年7月间110例接受索拉非治疗的进展期HCC患者,评价其疗效、不良反应,以总生存期和无肿瘤进展生存期为预后指标进行单因素和Cox比例风险模型多因素分析。  结果  110例患者随访中位时间9（2~18）个月,服用索拉非尼中位时间6.5（2~18）个月。14例（12.7%）获得完全缓解（CR）,16例（14.5%）部分缓解（PR）,40例（36.4%）病情稳定（SD）,总有效率为70例（63.6%）。中位生存期和无肿瘤进展生存期分别为10.5个月（95%CI:8.7~12.3）和5.0个月（95%CI:3.7~6.3）。多因素分析显示:联合局部治疗（肝动脉化疗栓塞或氩氦刀）、美国东部肿瘤协作组活动状态评分（Eastern Cooperative Oncology Group performance status score,ECOG PS）和Child-Pugh分级是影响无肿瘤进展生存时间的独立预后因素,而联合局部治疗、ECOG PS评分和AFP（alfa-fetopro? tein）水平是影响总生存期的独立预后因素。亚组分析显示:在肝癌进展组患者中继续服用索拉非尼其总生存期明显长于终止索拉非尼治疗者（11个月vs. 7.5个月,P < 0.001）。  结论  索拉非尼治疗进展期HCC,ECOG PS评分是影响生存期的一个重要因素,联合局部治疗有益于改善生存期。      

阿帕替尼用于一线治疗进展后晚期非鳞非小细胞肺癌的疗效和生存分析

背景与目的 晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的二线、三线化疗有效率较低,靶向药物的应用为部分患者带来生存获益.阿帕替尼是一种新型小分子抗血管生成药物,在多种恶性肿瘤治疗中展现出令人满意的抗癌活性.本研究旨在评价阿帕替尼用于一线治疗进展后晚期非鳞NSCLC的安全性和疗效.方法 回顾性分析128例晚期非鳞NSCLC不同治疗组患者的疗效和生存情况,用Kaplan-Meier法和Cox模型进行分析.结果 以单纯化疗组为对照,阿帕替尼单药组、单纯化疗组和阿帕替尼联合化疗组的中位无进展生存期(progression free survival,PFS)分别为3.0个月(P=0.381)、3.7个月和6.0个月(P<0.001),中位总生存期(overall survival,OS)分别为6.0个月(P=0.494)、6.5个月和9.0个月(P=0.001).3级-4级不良反应发生率分别为18.5%、15.8%和16.0%(P=0.947).治疗方案(P=0.018)及体能状态(performance status,PS)(P<0.001)是PFS的独立影响因素,吸烟史(P=0.014)、治疗方案(P=0.002)和PS(P<0.001)是OS的独立影响因素.结论 阿帕替尼安全性高,肺癌一线治疗失败后,二线或三线化疗联合阿帕替尼,与单纯化疗相比,患者有PFS和OS获益,阿帕替尼单药与单纯化疗组间PFS和OS无明显差异;无吸烟史、PS 0分-1分和联合治疗的患者预后更好.     

A multi-centre retrospective review of second-line therapy in advanced pancreatic adenocarcinoma

INTRODUCTION: Limited information on second-line treatment in patients with pancreatic adenocarcinoma is available. At time of first-line treatment failure, approximately half of the patients are candidates for further treatment. MATERIAL AND METHODS: A retrospective review of 183 patients submitted to second-line therapy has been performed to identify prognostic factors, provides useful information for patients counseling and generates hypotheses for future studies. Inclusion criteria were: cytological or histologic diagnosis of pancreatic adenocarcinoma and prior gemcitabine-including chemotherapy. Any age, performance status (PS) and chemotherapy regimen were considered. RESULTS: One hundred and eighty-three patients (106 males; 168 metastatic; median age 62 years; median PS 1; 63 submitted to prior curative surgery, 32 to prior radiotherapy) with a median previous progression-free survival (PFS) of 6.7 months were included. Median and 6-month PFS after initiation of salvage therapy were 3.0 months and 20%. Median, 1 and 2 years, overall survival after initiation of salvage therapy were 6.2 months, 17 and 4%, respectively. Previous PFS, CA19.9 levels and age independently predicted OS. CONCLUSION: Re-challenge with gemcitabine and 5-fluorouracil administration may have a role in selected patients.     

Comparison of second-line treatment outcomes between sensitive and refractory small cell lung cancer patients: a retrospective analysis

Purpose

Small cell lung cancer (SCLC) has a high relapse rate despite being very chemosensitive. The efficacy of second-line treatment is dismal. Our aim was to evaluate the outcome of second-line treatment.

Methods

We retrospectively assessed data of 120 SCLC patients who failed first-line treatment and received second-line treatment at three medical oncology centers.

Results

Median age of group was 58. 82 % had an ECOG PS of 0–1 at the time of relapse. 39 % were at limited stage (LS) at the time of diagnosis. Patients who progressed more than 3 months after first-line therapy were categorized as having platinum-sensitive disease (PSD) (64 %). The number of patients who received platin-based combination treatment was 33 (27 %). The median OS time starting from the initiation of second-line treatment was 7 months. Multivariate analysis identified PS (p = 0.006), extent of disease at diagnosis (0.014) and PSD (0.001) as the independent prognostic factors for survival. Subgroup analyses of the patients with PSD indicated platin rechallenge yields higher progression-free survival, overall survival and overall response rate.

Conclusion

Patients with good ECOG PS,who have PSD or initially presenting with LS, have a good prognosis and in patients with PSD, platinum-based therapy would be more appropriate.     

营养免疫炎性指标预测免疫联合放化疗二线治疗食管鳞癌患者预后的价值

  目的  评估营养免疫炎性指标用于预测接受camrelizumab联合放（化）疗二线治疗复发和（或）转移转移食管鳞癌（relapsed or metastatic esophageal squamous cell carcinoma ,R/M ESCC）患者预后的价值。  方法  从2018年1月至2021年3月,从河北医科大学第四医院筛选出48例符合入组标准的R/M ESCC患者进行回顾性分析,根据受试者工作特征曲线（receiver operating characteristic curve,ROC）确定预后营养指数（prognostic nutritional index, PNI）、中性粒细胞淋巴细胞比（neutrophilic-to-lymphocyte ratio,NLR）、血小板与淋巴细胞比（platelet-to-lymphocyte ratio,PLR）和全身免疫-炎症指数（systemic immune-inflammation index,SII）这4项指标预测患者预后的最佳临界值。应用SPSS 25.0版本软件进行单因素和多因素统计学分析。  结果  全组患者二线免疫治疗后的1、2年生存（overall survival,OS）率和无进展生存（progression-free survival,PFS）率分别为42.9%、22.5%和29.0%、5.8%;中位OS和PFS分别为9.0个月（95%CI：6.4～11.7）和8.5个月（95%CI：1.5～5.6）。多因素分析结果显示免疫联合方式、近期疗效、PNI、NLR、PLR和SII为患者OS的独立影响因素（P=0.044、0.030、<0.001、0.040、0.044、0.036）;免疫联合方式、使用免疫周期数、近期疗效、PNI、NLR、PLR和SII为患者PFS的独立影响因素（P=0.049、0.024、0.003、0.017、0.008、<0.001、0.009）。  结论  低PNL,高NLR、PLR和SII值为接受camrelizumab联合放（化）疗二线治疗R/M ESCC预后较差的独立性预测指标。     

Association of smoking with tumor size at diagnosis in non-small cell lung cancer

Background

Patients with small-cell lung cancer (SCLC) that progress after first-line chemotherapy have a poor prognosis and the evidence of a benefit from second-line (SL) chemotherapy is limited. Patients relapsing or progressing more than 90 days after completion of first-line treatment are considered platinum sensitive and may be rechallenged with platinum-based chemotherapy. Topotecan is approved as SL treatment independent of time to progression. This retrospective analysis evaluates the clinical outcomes of SCLC patients who received SL chemotherapy after platinum-etoposide chemotherapy.

Patients and methods

We retrospectively reviewed 161 patients who received SL chemotherapy for SCLC. Patients were divided into four subgroups by type of SL treatment: (1) platinum-based rechallenge; (2) anthracycline-based regimens; (3) topotecan; (4) other single agents. The endpoints were overall survival (OS), progression-free survival (PFS) and response rate (RR). Survival curves were plotted using the Kaplan-Meier method. The Cox proportional hazard model was used for multivariate analysis to investigate factors influencing survival.

Results

The median age was 63. There were 125 males and 36 females. Eastern Cooperative Oncology Group performance status (ECOG-PS) was 0, 1 and 2 in 12.5%, 62.5% and 25% of patients, respectively. Platinum sensitive/platinum resistant/platinum refractory/unknown = 121/29/3/8 patients. Median time to SL chemotherapy was 6.9 months.The median PFS from starting second-line treatment was 4.3 months and median OS was 5.8 months. The overall RR was 22.9%. There was a trend toward higher RR (34.5% vs 17.5%, p for trend: 0.06) and OS (9.2 months vs 5.8 months, p = 0.08) for patients with sensitive disease who were rechallenged with platinum-based chemotherapy.A multivariate analysis that adjusted for the time to SL treatment showed that a platinum-containing regimen achieves better RR, PFS and OS independently of the time to SL chemotherapy and that response to first-line treatment and PS at SL are the only independent prognostic factors.

Conclusions

The outcome for second-line therapy for SCLC was poor and benefit appeared to be limited to those patients with good PS and rechallenged with platinum-based chemotherapy. Platinum-based rechallenge should be considered as a standard comparator in future randomized controlled trials of SL chemotherapy.     

Efficacy of ramucirumab combination chemotherapy as second-line treatment in patients with advanced adenocarcinoma of the stomach or gastroesophageal junction after exposure to checkpoint inhibitors and chemotherapy as first-line therapy

FOLFOX plus nivolumab represents a standard of care for first-line therapy of advanced gastroesophageal cancer (aGEC) with positive PD-L1 expression. The efficacy of second-line VEGFR-2 inhibition with ramucirumab (RAM) plus chemotherapy after progression to immunochemotherapy remains unclear. Medical records of patients with aGEC enrolled in the randomized phase II AIO-STO-0417 trial after treatment failure to first-line FOLFOX plus nivolumab and ipilimumab were retrospectively analyzed. Patients were divided into two groups based on second-line therapy: RAM plus chemotherapy (RAM group) or treatment without RAM (control group). Eighty three patients were included. In the overall population, progression-free survival (PFS) in the RAM group was superior to the control (4.5 vs 2.9 months). Responders (CR/PR) to first-line immunochemotherapy receiving RAM containing second-line therapy had prolonged OS from start of first-line therapy (28.9 vs 16.5 months), as well as second-line OS (9.6 vs 7.5 months), PFS (5.6 vs 2.9 months) and DCR (53% vs 29%) compared to the control. PD-L1 CPS ≥1 was 42% and 44% for the RAM and the control, respectively. Patients with CPS ≥1 in the RAM group showed better tumor control (ORR 25% vs 10%) and improved survival (total OS 11.5 vs 8.0 months; second-line OS 6.5 vs 3.9 months; PFS 4.5 vs 1.6 months) compared to the control. Prior exposure to first-line FOLFOX plus dual checkpoint inhibition followed by RAM plus chemotherapy shows favorable response and survival rates especially in patients with initial response and positive PD-L1 expression and has the potential to advance the treatment paradigm in aGEC.     

Cisplatin and gemcitabine for advanced biliary tract cancer: a meta-analysis of two randomised trials

BackgroundTwo recent studies (ABC-02 [UK] and BT22 [Japan]) have demonstrated the superiority of cisplatin and gemcitabine (CisGem) chemotherapy over gemcitabine (Gem) alone for patients with pathologically proven advanced biliary tract cancer (BTC: cholangiocarcinoma, gallbladder and ampullary cancers). This pre-planned analysis evaluates the efficacy of CisGem with increased statistical power.Patients and methodsWe carried out a meta-analysis of individual patient-level data of these studies to establish the effect of CisGem versus Gem on progression-free survival (PFS), overall survival (OS) and carried out exploratory subgroup analyses.ResultsCisGem demonstrates a significant improvement in PFS [hazard ratio (HR) = 0.64, 95% confidence interval (CI) 0.53–0.76, P < 0.001] and OS (HR = 0.65, 95% CI 0.54–0.78, P < 0.001) over Gem. This effect is most marked among patients with good performance status (PS 0–1): HR for PFS is 0.61 (95% CI 0.51–0.74), P < 0.001 and OS HR = 0.64 (95% CI 0.53–0.77), P < 0.001. CisGem resulted in improved PFS and OS for intra- and extra-hepatic cholangiocarcinomas and gallbladder cancer. The treatment effect between UK and Japanese patients was consistent with respect to OS (HR = 0.65, 95% CI 0.53–0.79 and 0.65, 95% CI 0.42–1.03, respectively); with similar OS in the combination arms (median 11.7 and 11.1 months, respectively). Subgroups least likely to benefit included patients with ampullary tumours and poor performance status (PS2).ConclusionsCisGem is the standard of care for the first-line treatment of good-PS patients with advanced BTC regardless of ethnicity. Future studies should aim to enhance the effectiveness of this regimen in the first-line setting, establish the role of subsequent (second-line) therapy and assess the role of rationally developed molecular-targeted therapies.     

Nomogram Based on Monocyte-to-Lymphocyte Ratio to Predict Survival of Unresectable Esophageal Squamous Cell Carcinoma Who Receive First-Line PD-1/PD-L1 Inhibitors Combined with Chemotherapy

Background. Chemoimmunotherapy has become the first-line treatment for unresectable esophageal squamous cell carcinoma (ESCC). Still, reliable biomarkers to identify patients who could benefit from this combined therapy remain uncertain. This study focused on elucidating the predictive significance of the monocyte-to-lymphocyte ratio (MLR) and establishing the prognostic nomogram for unresectable ESCC treated with chemoimmunotherapy. Methods. Data of clinical features, peripheral blood parameters, and treatment records were collected in unresectable ESCC patients who received PD-1/PD-L1 inhibitors plus chemotherapy as the first-line treatment from September 2017 to August 2021. The nomogram based on MLR and clinical parameters for predicting the overall survival (OS) was developed and validated. Results. Out of 81 patients enrolled, patients with a lower MLR had significantly longer progression-free survival (PFS) and OS than patients with a higher pretreatment MLR (p = 0.0067; p = 0.00069). The OS nomogram integrating MLR, performance status (PS) score, and body mass index (BMI) achieved a C-index of 0.770 (95%CI 0.645–0.896). The area under the ROC curve (AUC) value of the nomogram predicting 12-, 18-, and 24-month OS rates were 0.855, 0.792, and 0.744, respectively, which were higher than the clinical TNM staging system or the MLR. Stratified by the nomogram-generated scores, three risk groups (low, moderate, and high) in survival curves manifested a distinct difference (p < 0.0001). Conclusion. MLR emerged as an independent predictive factor for PFS and OS in treatment-naive unresectable ESCC patients treated with chemoimmunotherapy. The constructed nomogram of MLR and clinical parameters was a reliable model for prognostic estimation.     

Final results of the TANIA randomised phase III trial of bevacizumab after progression on first-line bevacizumab therapy for HER2-negative locally recurrent/metastatic breast cancer

BackgroundThe randomised phase III TANIA trial demonstrated that continuing bevacizumab with second-line chemotherapy for locally recurrent/metastatic breast cancer (LR/mBC) after progression on first-line bevacizumab-containing therapy significantly improved progression-free survival (PFS) compared with chemotherapy alone [hazard ratio (HR) = 0.75, 95% confidence interval (CI) 0.61–0.93]. We report final results from the TANIA trial, including overall survival (OS) and health-related quality of life (HRQoL).Patients and methodsPatients with HER2-negative LR/mBC that had progressed on or after first-line bevacizumab plus chemotherapy were randomised to receive standard second-line chemotherapy either alone or with bevacizumab. At second progression, patients initially randomised to bevacizumab continued bevacizumab with their third-line chemotherapy, but those randomised to chemotherapy alone were not allowed to cross over to receive third-line bevacizumab. The primary end point was second-line PFS; secondary end points included third-line PFS, combined second- and third-line PFS, OS, HRQoL and safety.ResultsOf the 494 patients randomised, 483 received second-line therapy; 234 patients (47% of the randomised population) continued to third-line study treatment. The median duration of follow-up at the final analysis was 32.1 months in the chemotherapy-alone arm and 30.9 months in the bevacizumab plus chemotherapy arm. There was no statistically significant difference between treatment arms in third-line PFS (HR = 0.79, 95% CI 0.59–1.06), combined second- and third-line PFS (HR = 0.85, 95% CI 0.68–1.05) or OS (HR = 0.96, 95% CI 0.76–1.21). Third-line safety results showed increased incidences of proteinuria and hypertension with bevacizumab, consistent with safety results for the second-line treatment phase. No differences in HRQoL were detected.ConclusionsIn this trial, continuing bevacizumab beyond first and second progression of LR/mBC improved second-line PFS, but no improvement in longer term efficacy was observed. The second-line PFS benefit appears to be achieved without detrimentally affecting quality of life.ClinicalTrials.govNCT01250379.     

帕博利珠单抗治疗复发/转移性头颈部鳞状细胞癌患者的预后与营养因素的相关性分析

  目的  探究接受帕博利珠单抗二线治疗复发/转移性（recurrent/metastatic, R/M）头颈部鳞状细胞癌（head and neck squamous cell carcinoma,HNSCC）患者的临床相关营养因素与预后的相关性。  方法  回顾性分析2019年1月至2021年6月上海交通大学医学院附属第九人民医院收治的86例接受帕博利珠单抗治疗的R/M HNSCC患者,对其进行生存预后分析和危险因素评估。  结果  中位随访时间11.6（3.0～25.9）个月,中位总生存期（overall survival,OS）11.3个月,中位无进展生存期（progression-free survival,PFS）8.3个月。多因素分析显示,体质量不足（OS:P=0.016;PFS:P=0.003）、年龄≥60岁（OS:P=0.009;PFS:P=0.014）、低白蛋白（OS:P=0.013;PFS:P=0.010）、体力状态（PS）评分≥2分（OS:P＜0.001;PFS:P=0.005）、联合阳性评分（CPS）<1（OS:P=0.009;PFS:P=0.006）及临床分期rⅣ期（OS:P=0.011;PFS:P=0.003）是死亡风险增加的独立风险因素。超重是减少死亡风险的指标（OS:P=0.001;PFS:P=0.004）。Kaplan-Meier生存曲线分析显示,BMI及血清白蛋白与OS及PFS显著相关（P<0.001）。  结论  BMI、年龄、血清白蛋白、PS评分、CPS评分、临床分期与接受帕博利珠单抗治疗的R/M HNSCC患者预后显著相关,可作为R/M HNSCC患者抗PD-1治疗的独立预后预测指标。      

Epidermal growth factor receptor-tyrosine kinase inhibitor therapy is effective as first-line treatment of advanced non-small-cell lung cancer with mutated EGFR: A meta-analysis from six phase III randomized controlled trials

Gefiinib and erlotinib are two similar small molecules of selective and reversible epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), which have been approved for second-line or third-line indication in previously treated advanced Non-small-cell lung cancer (NSCLC) patients. The results of comparing the EGFR-TKI with standard platinum-based doublet chemotherapy as the first-line treatment in advanced NSCLC patients with activated EGFR mutation were still controversial. A meta-analysis was performed to derive a more precise estimation of these regimens. Finally, six eligible trials involved 1,021 patients were identified. The patients receiving EGFR-TKI as front-line therapy had a significantly longer progression-free survival (PFS) than patients treated with chemotherapy [median PFS was 9.5 versus 5.9 months; hazard ratio (HR)=0.37; 95% confidence intervals (CI)=0.27-0.52; p<0.001]. The overall response rate (ORR) of EGFR-TKI was 66.60%, whereas the ORR of chemotherapy regimen was 30.62%, which was also a statistically significant favor for EGFR-TKI [relative risk (RR)=5.68; 95% CI=3.17-10.18; p<0.001]. The overall survival (OS) was numerically longer in the patients received EGFR-TKI than patients treated by chemotherapy, although the difference did not reach a statistical significance (median OS was 30.5 vs. 23.6 months; HR=0.94; 95% CI=0.77-1.15; p=0.57). Comparing with first-line chemotherapy, treatment of EGFR-TKI achieved a statistical significantly longer PFS, higher ORR and numerically longer OS in the advanced NSCLC patients harboring activated EGFR mutations, thus, it should be the first choice in the previously untreated NSCLC patients with activated EGFR mutation.     

Prognosis and chemosensitivity of deficient MMR phenotype in patients with metastatic colorectal cancer: An AGEO retrospective multicenter study

Mismatch repair-deficient (dMMR) and/or microsatellite instability-high (MSI) colorectal cancers (CRC) represent about 5% of metastatic CRC (mCRC). Prognosis and chemosensitivity of dMMR/MSI mCRC remain unclear. This multicenter study included consecutive patients with dMMR/MSI mCRC from 2007 to 2017. The primary endpoint was the progression-free survival (PFS) in a population receiving first-line chemotherapy. Associations between chemotherapy regimen and survival were evaluated using a Cox regression model and inverse of probability of treatment weighting (IPTW) methodology in order to limit potential biases. Overall, 342 patients with dMMR/MSI mCRC were included. Median PFS and overall survival (OS) on first-line chemotherapy were 6.0 and 26.3 months, respectively. For second-line chemotherapy, median PFS and OS were 4.4 and 21.6 months. Longer PFS (8.1 vs. 5.4 months, p = 0.0405) and OS (35.1 vs. 24.4 months, p = 0.0747) were observed for irinotecan-based chemotherapy compared to oxaliplatin-based chemotherapy. The association was no longer statistically significant using IPTW methodology. In multivariable analysis, anti-VEGF as compared to anti-EGFR was associated with a trend to longer OS (HR = 1.78, 95% CI 1.00–3.19, p = 0.0518), whatever the backbone chemotherapy used. Our study shows that dMMR/MSI mCRC patients experienced short PFS with first-line chemotherapy with or without targeted therapy. OS was not different according to the chemotherapy regimen used, but a trend to better OS was observed with anti-VEGF. Our study provides some historical results concerning chemotherapy in dMMR/MSI mCRC in light of the recent nonrandomized trials with immune checkpoint inhibitors.     

Real-World Pattern of Treatment and Clinical Outcomes of EGFR-Mutant Non-Small Cell Lung Cancer in a Single Academic Centre in Quebec

The discovery of EGFR tyrosine kinase inhibitors (TKI) for the treatment of EGFR mutant (EGFRm) metastatic NSCLC is regarded as a landmark in lung cancer. EGFR-TKIs have now become a standard first-line treatment for EGFRm NSCLC. The aim of this retrospective cohort study is to describe real-world patterns of treatment and treatment outcomes in patients with EGFRm metastatic NSCLC who received EGFR-TKI therapy outside of clinical trials. One hundred and seventy EGFRm metastatic NSCLC patients were diagnosed and initiated on first-line TKI therapy between 2004 and 2018 at the Peter Brojde Lung Cancer Centre in Montreal. Following progression of the disease, 137 (80%) patients discontinued first-line treatment. Moreover, 80/137 (58%) patients received second-line treatment, which included: EGFR-TKIs, platinum-based, or single-agent chemotherapy. At the time of progression on first-line treatment, 73 patients were tested for the T790M mutation. Moreover, 30/73 (41%) patients were found to be positive for the T790M mutation; 62/80 patients progressed to second-line treatment and 20/62 were started on third-line treatment. The median duration of treatment was 11.5 (95% CI; 9.62–13.44) months for first-line treatment, and 4.4 (95% CI: 1.47–7.39) months for second-line treatment. Median OS from the time of diagnosis of metastatic disease was 23.5 months (95% CI: 16.9–30.1) and median OS from the initiation of EGFR-TKI was 20.6 months (95% CI: 13.5–27.6). We identified that ECOG PS ≤ 2, presence of exon 19 deletion mutation, and absence of brain metastases were associated with better OS. A significant OS benefit was observed in patients treated with osimertinib in second-line treatment compared to those who never received osimertinib. Overall, our retrospective observational study suggests that treatment outcomes in EGFRm NSCLC in real-world practice, such as OS and PFS, reflect the result of RCTs. However, given the few observational studies on real-world treatment patterns of EGFR-mutant NSCLC, this study is important for understanding the potential impact of EGFR-TKIs on survival outside of clinical trials. Further real-world studies are needed to characterize patient outcomes for emerging therapies, including first-line osimertinib use and combination of osimertinib with chemotherapy and potential future combination of osimertinib and novel anticancer drug, outside of a clinical trial setting.