Chemotherapy Progression-free Survival Research Articles

VIC regimen (vemurafenib/irinotecan/cetuximab) versus bevacizumab plus chemotherapy as first-line treatment for BRAF V600E-mutated advanced colorectal cancer.

3596 Background: The need for safe and effective therapies for untreated, BRAF V600E-mutated, unresectable locally advanced or metastatic colorectal cancer remains unmet. The purpose of this study was to compare the efficacy and safety of the VIC (Vemurafenib/Irinotecan/Cetuximab) regimen versus bevacizumab plus chemotherapy as first-line setting in Asian patients. Methods: In the single-center prospective cohort study, 78 untreated, BRAF V600E-mutant, locally advanced or metastatic CRC patients were enrolled. Every two weeks, the VIC regimen and bevacizumab plus doublet or triplet chemotherapy are administered. We evaluated the objective response rate (ORR), the disease control rate (DCR), and the conversion resection rate. In progression-free survival (PFS) and overall survival, the Kaplan-Meier method was utilized (OS). Results: In the evaluable population, 32 patients received VIC regimen and 35 patients received bevacizumab plus chemotherapy. The ORR and DCR in the VIC group were significantly higher than in the bevacizumab-therapy group (ORR: 68.8% versus 40.0%, P = 0.018; DCR: 100.0% versus 80.0%, P = 0.023). The VIC regimen was significantly superior to bevacizumab plus chemotherapy for PFS (median, 11.9 vs 7.9 months; hazard ratio [HR] = 0.48, 95% CI, 0.27-0.87; P = 0.012) and OS (median, 24.5 vs 14.4 months; HR = 0.36, 95% CI, 0.16-0.78; P = 0.007). In the VIC group, the conversion resection rate for liver metastases was 42.1% (8 of 19 patients), and for local CRC it was 66.7% (6 of 9 patients with initially unresectable local CRC). Rates of treatment-related adverse events of Grade 3 to 4 were 32.4% and 31.1% for the VIC regimen and bevacizumab plus chemotherapy, respectively. Conclusions: Among Asian patients with BRAF V600E-mutated advanced CRC, the VIC regimen was superior to bevacizumab plus chemotherapy in terms of tumor response and oncological survival, with a tolerable and manageable toxicity profile in the first-line setting. Clinical trial information: NCT05540951 .

SOGUG-vexillum: Phase II non-randomized clinical trial of nivolumab/ipilimumab maintenance following first-line chemotherapy in unresectable locally advanced or metastatic urothelial cancer.

TPS4606 Background: The current standard of care in non-progressors to first-line platinum-based chemotherapy for unresectable locally advanced or metastatic urothelial carcinoma (UC) is maintenance treatment with avelumab plus best supportive care (BSC). The Checkmate 032 trial showed that the highest ORR (42.4%) was achieved by the combination of Nivolumab 1 mg/kg and Ipilimumab 3 mg/kg in refractory mUC (1), with a manageable safety profile and better outcomes compared to other treatment arms. The trial aims to consolidate the clinical benefit achieved from first-line chemotherapy with the combination of nivolumab 1mg/kg plus ipilimumab 3mg/kg followed by nivolumab. Methods: This single arm, open-label, multicenter study evaluates the effectiveness of Ipilimumab and nivolumab followed by nivolumab maintenance therapy in delaying disease progression in patients with unresectable urothelial cancer that did not progress after first-line chemotherapy. Main eligibility criteria include: Male or female subjects ≥ 18 yrs old with written informed consent, ECOG performance status 0 or 1, unresectable locally advanced or metastatic transitional cell carcinoma of the urothelium (UCC), patient inclusion within 3-12 weeks after the last chemo dose, no progressive disease per RECIST v1.1, available tumor tissue at baseline, adequate normal organ and marrow function (Haemoglobin ≥ 9.0 g/dL, ANC > 1500 per mm3, platelets ≥ 100,000 per mm3, bilirubin ≤ 1.5 X ULN, transaminases ≤ 2.5X ULN, creatinine clearance > 30 mL/min). The primary endpoint is Progression Free Survival (PFS). Secondary objectives include: objective response rate (ORR), duration of response (DoR), overall survival (OS), chemotherapy overall survival (cOS), and chemotherapy progression-free survival (cPFS). Additionally, the study also has safety secondary objectives. Dynamic biomarker analysis will be performed. As of January 2023, 5 out of the planned 66 patients have been enrolled in the study. 1) Sharma P et al. J Clin Oncol. 2019. Clinical trial information: EudraCT 2021-005364-22 .

Checkpointinhibitoren beim kolorektalen Karzinom – eine neue Ära?

Checkpoint-inhibitors have shown high response rates in some tumours such as melanomas. This article describes the data concerning the efficacy of checkpoint inhibitors in patients with colorectal cancer (CRC). Efficacy for the use of checkpoint inhibitors in CRC has only been shown for tumours with high microsatellite instability (MSI-H) or adeficient mismatch repair system (dMMR). The proportion of patients with MSI-H/dMMR cancers is 10-12% in colon cancers and 3% in rectal cancers. In cohort studies with patients that had progressed under at least one chemotherapy aresponse rate of 33% could be shown for pembrolizumab and 65% for the combination nivolumab and ipilimumab. In many patients the response was long-lasting. After 2years between 55and 75% of patients were still alive. In arandomized study comparing first-line therapy with pembrolizumab and chemotherapy progression-free survival was much longer for the pembrolizumab group (16.5 vs. 8.2months). In asmall series of patients with MSI-H/dMMR rectal cancers treatment with dostarlimab resulted in complete remission in all patients with no regrowth during an admittedly short follow-up. Aseries of patients with locally advanced MSI-H/dMMR colon cancers showed atreatment response in nearly all patients with 67% experiencing complete remission. In patients with microsatellite-stable (MSS) cancers checkpoint inhibitors showed no effect, the combination with chemotherapy at most amodest effect. Checkpoint inhibitors are the first-choice palliative treatment in patients with MSI-H/dMMR CRC and have replaced chemotherapy as the first option. Early data show ahigh response rate for the neoadjuvant treatment of MSI-H/dMMR rectal and colon cancers.

Clinical management of metastatic hormone receptor-positive, HER2-negative breast cancer (MBC) after CDK 4/6 inhibitors: a retrospective single-institution study.

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6is), in combination with endocrine therapy (ET), are standard either in the first (1L) or second-line (2L) setting for the treatment of hormone receptor (HR) positive, HER2-negative metastatic breast cancer (MBC). However, the optimal sequencing of treatments after progression on CDK4/6i remains unknown. We performed a single-institution analysis to identify treatments and outcomes after progression on a CDK4/6i. We identified patients with HR-positive, HER2-negative MBC prescribed a CDK4/6i in the 1L or 2L settings from December 2014 to February 2018 at Mayo Clinic in Rochester, Minnesota. Outcomes were collected through September 30, 2020. Palbociclib, in combination with letrozole or fulvestrant, was the most prescribed CDK4/6i. The 1L and 2L CDK4/6i cohorts exhibited comparable overall survival (OS), but progression-free survival (PFS) was longer in the 1L than the 2L cohort [28.2months (95% CI 19.6-34.9) vs 19.8months (95% CI 15.7-29.6)]. The most common post-CDK4/6i treatments were PI3K/mTOR inhibitors (PI3K/mTORi), single-agent ET, or chemotherapy. PFS in the 1L CDK4/6i cohort following PI3K/mTORi was 8.5months (95% CI 5.5months-NE), single-agent ET was 6.0months (95% CI 3.3-14.0months), and chemotherapy PFS was 5.4months (95% CI 3.3months-NE). Following progression on a CDK 4/6i, mPFS was short, with similar PFS times comparing chemotherapy and ET, with slightly longer PFS for targeted strategies (PI3K/mTOR). These results highlight a major need to better understand the mechanisms of CDK4/6i resistance and identify new therapeutic strategies for these patients.

Does HER2 status influence in the benefit of ramucirumab and paclitaxel as second line treatment of advanced gastro-esophageal adenocarcinoma? Data from the AGAMENON-SEOM registry.

This study aimed to compare ramucirumab-paclitaxel versus chemotherapy in second-line (2L) advanced gastroesophageal cancer (aGEC) based on HER2 status and analyze prognostic factors. The study includes patients from the AGAMENON-SEOM registry with aGEC and known HER2 status who received 2L between 2016 and 2021. The Kaplan-Meier method was used to calculate progression-free survival (PFS) and overall survival (OS) and multivariable Cox regression analysis was done to adjust for confounding variables. Of the 552 patients who met the selection criteria, 149 (26.9%) had HER2-positive aGEC, 89 were treated with chemotherapy, and 60 with ramucirumab-paclitaxel, and 403 had an HER2-negative aGEC, 259 were treated with chemotherapy, and 144 with ramucirumab-paclitaxel. In the whole sample, 2L PFS was 3.0months (95% CI 2.8-3.2), 2L OS, 5.7months (5.2-6.3), and ramucirumab-paclitaxel versus chemotherapy was associated with increased PFS (HR 0.64, 95% CI 0.53-0.78, p < 0.0001) and OS (HR 0.68, 0.55-0.83, p = 0.0002). Median PFS of ramucirumab- paclitaxel versus chemotherapy was 3.5 vs 2.8months (HR 0.67, 0.54-0.83, p = 0.0004) in HER2-negative, and 4.7 vs 2.7months (HR 0.57, 0.40-0.82, p = 0.0031) in HER2-positive aGEC, respectively. Median OS for ramucirumab-paclitaxel versus chemotherapy was 6.6 vs 5months (HR 0.67, 0.53-0.85, p = 0.0007) in HER2-negative, and 7.4 vs 5.6months (HR 0.70, 0.53-1.04, p = 0.083) in HER2-positive aGEC, respectively. ECOG-PS, tumor burden, Lauren subtype, and neutrophil-lymphocyte ratio were prognostic factors. In patients with an aGEC from the AGAMENON-SEOM registry, 2L treatment with ramucirumab-paclitaxel was superior to chemotherapy in PFS, OS and response rate, independent of HER2 status.

The prognostic value of chemotherapy or endocrine therapy choice according to circulating tumor cell count in HR+HER2- metastatic breast cancer: a retrospective study.

BackgroundCirculating tumor cell (CTC) count have prognostic role for metastatic breast cancer (MBC). No clear biomarkers can guide selection of chemotherapy (CT) or endocrine therapy (ET) in 1st-line setting of hormone-receptor positive and human epidermal growth factor receptor 2 negative (HR+HER2−) MBC. The present study investigated the prognostic role CT or ET according to the CTC count in HR+HER2− MBC.MethodsWe consecutively collected the data of 53 HR+HER2− MBC patients who received 1st-line CT or ET, who had CTC count detected by our peptide-based nanomagnetic CTC isolation system (Pep@MNPs) from January 2014 to December 2015. The clinicopathological characteristics according the CTC count and 1st-line ET vs. CT were compared. Follow-up was conducted every 6 months. The primary endpoint was progression-free survival (PFS) and overall survival (OS). A Cox regression analysis was conducted to determine the prognostic roles of CTC and 1st-line therapy of ET vs. CT for PFS and OS.ResultsThe median CTC count of the 53 patients was 2 (range, 0–18). The clinicopathological characteristics of the patients in the CTC count <2 group and the CTC count ≥2 group were similar. The patients with a CTC count <2 had a significantly longer PFS than those with a CTC count ≥2 (P=0.005, hazard ratio =4.138, 12.1 vs. 7.1 months). The patients who received CT had a significantly longer PFS than those who received ET (P=0.041, hazard ratio =2.721, 9.9 vs. 7.2 months). In the CTC count ≥2 group, the patients who received CT had a significantly longer PFS than those who received ET (P=0.048, hazard ratio =2.475, 8.7 vs. 6.3 months). In the CTC count <2 group, there was no significant difference in PFS between the CT and ET groups (P=0.071). Additionally, the CTC count had no significant effect on OS (P=0.116, hazard ratio =2.391, 54.2 vs. 34.2 months).ConclusionsThe present study showed that CTC count determined by the Pep@MNP system confirmed the prognostic value in the HR+HER2− MBC patients. And it might be helpful in choosing a 1st-line treatment of CT or ET for HR+HER2− MBC patients.

Real-world application of tumor mutational burden-high (TMB-high) and microsatellite instability (MSI) confirms their utility as immunotherapy biomarkers

IntroductionMicrosatellite instability (MSI) testing and tumor mutational burden (TMB) are genomic biomarkers used to identify patients who are likely to benefit from immune checkpoint inhibitors. Pembrolizumab was recently approved by the Food and Drug Administration for use in TMB-high (TMB-H) tumors, regardless of histology, based on KEYNOTE-158. The primary objective of this retrospective study was real-world applicability and use of immunotherapy in TMB/MSI-high patients to lend credence to and refine this biomarker.MethodsCharts of patients with advanced solid tumors who had MSI/TMB status determined by next generation sequencing (NGS) (FoundationOne CDx) were reviewed. Demographics, diagnosis, treatment history, and overall response rate (ORR) were abstracted. Progression-free survival (PFS) was determined from Kaplan–Meier curves. PFS1 (chemotherapy PFS) and PFS2 (immunotherapy PFS) were determined for patients who received immunotherapy after progressing on chemotherapy. The median PFS2/PFS1 ratio was recorded.ResultsMSI-high or TMB-H [≥20 mutations per megabase (mut/MB)] was detected in 157 adults with a total of 27 distinct tumor histologies. Median turnaround time for NGS was 73 days. ORR for most recent chemotherapy was 34.4%. ORR for immunotherapy was 55.9%. Median PFS for patients who received chemotherapy versus immunotherapy was 6.75 months (95% confidence interval, 3.9-10.9 months) and 24.2 months (95% confidence interval, 9.6 months to not reached), respectively (P = 0.042). Median PFS2/PFS1 ratio was 4.7 in favor of immunotherapy.ConclusionThis real-world study reinforces the use of TMB as a predictive biomarker. Barriers exist to the timely implementation of NGS-based biomarkers and more data are needed to raise awareness about the clinical utility of TMB. Clinicians should consider treating TMB-H patients with immunotherapy regardless of their histology.

Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study

First-line therapy for advanced oesophageal cancer is currently limited to fluoropyrimidine plus platinum-based chemotherapy. We aimed to evaluate the antitumour activity of pembrolizumab plus chemotherapy versus chemotherapy alone as first-line treatment in advanced oesophageal cancer and Siewert type 1 gastro-oesophageal junction cancer. We did a randomised, placebo-controlled, double-blind, phase 3 study across 168 medical centres in 26 countries. Patients aged 18 years or older with previously untreated, histologically or cytologically confirmed, locally advanced, unresectable or metastatic oesophageal cancer or Siewert type 1 gastro-oesophageal junction cancer (regardless of PD-L1 status), measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1, and Eastern Cooperative Oncology Group performance status of 0-1, were randomly assigned (1:1) to intravenous pembrolizumab 200 mg or placebo, plus 5-fluorouracil and cisplatin (chemotherapy), once every 3 weeks for up to 35 cycles. Randomisation was stratified by geographical region, histology, and performance status. Patients, investigators, and site staff were masked to group assignment and PD-L1 biomarker status. Primary endpoints were overall survival in patients with oesophageal squamous cell carcinoma and PD-L1 combined positive score (CPS) of 10 or more, and overall survival and progression-free survival in patients with oesophageal squamous cell carcinoma, PD-L1 CPS of 10 or more, and in all randomised patients. This trial is registered with ClinicalTrials.gov, NCT03189719, and is closed to recruitment. Between July 25, 2017, and June 3, 2019, 1020 patients were screened and 749 were enrolled and randomly assigned to pembrolizumab plus chemotherapy (n=373 [50%]) or placebo plus chemotherapy (n=376 [50%]). At the first interim analysis (median follow-up of 22·6 months), pembrolizumab plus chemotherapy was superior to placebo plus chemotherapy for overall survival in patients with oesophageal squamous cell carcinoma and PD-L1 CPS of 10 or more (median 13·9 months vs 8·8 months; hazard ratio 0·57 [95% CI 0·43-0·75]; p<0·0001), oesophageal squamous cell carcinoma (12·6 months vs 9·8 months; 0·72 [0·60-0·88]; p=0·0006), PD-L1 CPS of 10 or more (13·5 months vs 9·4 months; 0·62 [0·49-0·78]; p<0·0001), and in all randomised patients (12·4 months vs 9·8 months; 0·73 [0·62-0·86]; p<0·0001). Pembrolizumab plus chemotherapy was superior to placebo plus chemotherapy for progression-free survival in patients with oesophageal squamous cell carcinoma (6·3 months vs 5·8 months; 0·65 [0·54-0·78]; p<0·0001), PD-L1 CPS of 10 or more (7·5 months vs 5·5 months; 0·51 [0·41-0·65]; p<0·0001), and in all randomised patients (6·3 months vs 5·8 months; 0·65 [0·55-0·76]; p<0·0001). Treatment-related adverse events of grade 3 or higher occurred in 266 (72%) patients in the pembrolizumab plus chemotherapy group versus 250 (68%) in the placebo plus chemotherapy group. Compared with placebo plus chemotherapy, pembrolizumab plus chemotherapy improved overall survival in patients with previously untreated, advanced oesophageal squamous cell carcinoma and PD-L1 CPS of 10 or more, and overall survival and progression-free survival in patients with oesophageal squamous cell carcinoma, PD-L1 CPS of 10 or more, and in all randomised patients regardless of histology, and had a manageable safety profile in the total as-treated population. Merck Sharp & Dohme.

Feasibility and safety of PD-1/L1 inhibitors for non-small cell lung cancer in front-line treatment: a Bayesian network meta-analysis.

BackgroundThis Bayesian network meta-analysis (NMA) was conducted to compare efficacy and safety of programmed death 1/ligand 1 (PD-1/L1) inhibitors in previous untreated advanced non-small cell lung cancer (NSCLC) patients.MethodsEligible studies evaluating first-line anti-PD-1/L1 based regimens in advanced NSCLC patients were included. Overall survival (OS), progression free survival (PFS), objective response rate (ORR), as well as treatment-related severe adverse events (tr-SAE) were synthesized within the Bayesian framework. Subgroup analysis was conducted according to PD-L1 expression.ResultsTwelve studies including 7,490 patients and 9 treatment strategies were enrolled in this study. For the PD-L1 expression non-selective patients, all chemo-immunotherapies were significantly better than chemotherapy for prolonging OS and PFS, except for caremlizumab plus chemotherapy (HR =0.72) failed to show advantages for OS. In addition, pembrolizumab plus chemotherapy showed better PFS than nivolumab plus ipilimumab (HR =0.66). In PD-L1 ≥50% patients, all immunotherapy was better than chemotherapy for OS, except for nivolumab (HR =0.83) and nivolumab plus ipilimumab (HR =0.70). For PFS, pembrolizumab plus chemotherapy (HR =0.39), atezolizumab plus chemotherapy (HR =0.47) and pembrolizumab (HR =0.67) were significantly better than chemotherapy. In PD-L1 1–49% patients, pembrolizumab plus chemotherapy (HR =0.52) and atezolizumab plus chemotherapy (HR =0.70) were better than chemotherapy for PFS. In the PD-L1 positive or negative group, all included corresponding regimens were equivalence according to OS and PFS.ConclusionsWe conducted a systematic comparison of first line immunotherapy for advanced NSCLC. Chemo-immunotherapies were better than chemotherapy and mono-immunotherapies in most patients. Pembrolizumab might have better efficacy than other PD-1/L1 inhibitors.

Do systemic treatments delivered after Nivolumab result in better outcomes? A bicentric case-control study

BackgroundImmune checkpoint inhibitors (ICI) are now widely used at different stages of non-small cell lung cancers (NSCLC). Some clinical studies suggest that chemotherapy and immunotherapy have synergic activities, raising the question of the best therapeutic sequence. We studied the effect of chemotherapy in advanced NSCLC when administered after immunotherapy by nivolumab. MethodsWe performed a bicentric, retrospective, case-control study in two French hospitals. Patients with NSCLC treated with chemotherapy after nivolumab between January 2015 and January 2016 were included. Each case was matched on age and number of previous lines to one lung cancer patient who had not received nivolumab. Each CT-scanner has been reviewed and the objective response to chemotherapy was assessed for each patient according to the RECIST 1.1 criteria. ResultsThirty-one patients with advanced NSCL who had at least received one cycle of chemotherapy after progression under nivolumab in the inclusion period were matched to 31 controls. The median age for cases was 59 yo and the predominant tumoral histology was adenocarcinoma (77%). The progression free survival (PFS) was 2.95 months in the studied group vs 2.69 months (P=0.18) in the control group. At best response, disease control (DC=partial response and stable disease) was better in the case group than in the control group (58% vs 39%, P=0.127). Cases were about five times more likely to get objective response to best evaluation than controls (OR=5.043 [95% CI: 0.975–26.086]; P=0.054). The overall survival (OS) was 7.3 months in the case group and 3.3 months in the control group (P=0.074). Patients who have been treated with targeted therapy instead of chemotherapy and patients with squamous lung cancer had worst PFS and OS. ConclusionIn advanced NSCLC, the chemotherapy progression free survival does not seem higher when administered after nivolumab. However, when administered post-nivolumab, traditional chemotherapy has 5 times more chances to achieve objective response and seems to improve overall survival of cases. Pooled analysis with other similar studies might be interesting for a next step.

P3.01-016 Factors Associated with Symptoms Improvement and HRQoL for First-Line EGFR-TKIs in NSCLC: A Multicenter Prospective SMILE Study

First-line epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) offer an advantage compared to doublet chemotherapy in progression free survival, tolerability, and quality of life (QOL) in EGFR-mutated advanced non-small cell lung cancer (NSCLC) patients. In Taiwan, gefitinib, erlotinib and afatinib are all reimbursed as first-line therapy. It provides a rare opportunity to investigate factors associated with the extent of symptoms and QOL improvement in real-world patient population.

Clinical significance of circulating tumor cells in patients with small-cell lung cancer.

This study investigated the correlation of the presence of circulating tumor cells (CTCs) with clinical characteristics, and the predictive value of CTCs for progression-free survival (PFS) in patients with small-cell lung cancer (SCLC). Samples were obtained from 42 patients with SCLC before and after the first cycle of chemotherapy. CTCs were quantitated by negative immunomagnetic enrichment and immunocytochemistry using anti-CD45 and anti-pancytokeratin antibodies. CTCs were positive (≥2) in 76.19% of patients with SCLC and negative in the control group. The presence of CTCs was positively correlated with 6 clinical characteristics. PFS was 6.055 and 10.670 months for patients with ≥2 and <2 CTCs/7.5 mL of blood before chemotherapy; after chemotherapy PFS was 4.862 and 10.535 months, respectively. This study showed that both baseline CTC numbers and the change in CTC numbers after 1 cycle of chemotherapy are significant prognostic factors of PFS for SCLC.

Efficacy of surgery and rituximab in primary gastric diffuse large B-cell lymphoma

目的探讨手术联合化疗与单纯化疗对原发胃弥漫大B细胞淋巴瘤（PGDLBCL）患者生存的影响，并分析化疗过程中联合应用利妥昔单抗（R）对其预后的影响。方法回顾性分析83例PGDLBCL患者的临床资料，并分析外科手术及利妥昔单抗对患者生存的影响。结果83例患者中男43例，女40例，中位年龄52 (20~76）岁，中位随访时间为36 (4~59）个月。手术联合化疗组（40例）和单纯化疗组（43例）患者的5年总生存（OS）率分别为68.4%、85.9%（P=0.117），疾病无进展生存（PFS）率分别为66.7%、82.6%（P=0.258），差异均无统计学意义。手术联合化疗患者中R-CHOP方案组（23例）和CHOP方案组（17例）患者的5年OS率分别为73.6%、64.2%（P=0.113），PFS率分别为71.2%、62.5%（P= 0.147）；单纯化疗患者中R-CHOP方案组（24例）和CHOP方案组（19例）患者的5年OS率分别为85.7%、83.5%（P=0.152），PFS率分别为83.4%、81.8%（P=0.307）。单纯化疗组和手术联合化疗组Lugano分期早期（Ⅰ~Ⅱ1期）患者的5年OS率分别为86.4%、78.7%，差异无统计学意义（P=0.283）；晚期（Ⅱ2~Ⅳ期）患者分别为74.6%、58.5%，差异有统计学意义（P=0.040）。多因素分析显示IPI评分是影响预后的独立因素（RR=0.370，95% CI 0.089~3.537，P=0.015）。结论单纯化疗或手术联合化疗对PGDLBCL患者长期生存的影响差异无统计学意义，但由于手术可能造成患者生存质量的下降，因此对于无手术指征者更倾向于推荐单纯化疗。本研究中利妥昔单抗的联合应用未能使大部分这类患者的生存显著获益，但这需要进一步多中心、大样本的研究来证实。

The Efficacy of Single-Agent Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy in Biologically Selected Patients with Non-Small-Cell Lung Cancer: A Meta-Analysis of 19 Randomized Controlled Trials

Objective: To determine the efficacy of first-generation single-agent epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy in advanced non-small-cell lung cancer patients with known EGFR mutation status, we undertook this pooled analysis. Method: We searched for randomized controlled trials (RCTs) in Medline, Embase, the Cochrane Controlled Trials Register, the Science Citation Index, and the American Society of Clinical Oncology annual meetings. Results: Out of 2,129 retrieved articles, 19 RCTs enrolling 2,016 patients with wild-type EGFR tumors and 1,034 patients with mutant EGFR tumors were identified. For these EGFR mutant patients, single-agent EGFR-TKI therapy improved progression-free survival (PFS) over chemotherapy: the summary hazard ratios (HRs) were 0.41 (p < 0.001) for the first-line setting and 0.46 (p = 0.02) for the second-/third-line setting. For those EGFR wild-type patients, single-agent EGFR-TKI therapy did not do as well as chemotherapy in the first-line setting (HR = 1.65, p = 0.03) and in the second-/third-line setting (HR = 1.27, p = 0.006). No statistically significant difference was observed in terms of overall survival (OS). Using platinum-based doublet chemotherapy as a common comparator, indirect comparison showed the superior efficacy of single-agent EGFR-TKI therapy over EGFR-TKIs added to chemotherapy in PFS [HR = 1.35 (1.03, 1.77), p = 0.03]. Additionally, a marginal trend towards the same direction was found in the OS analysis [HR = 1.16 (0.99, 1.35), p = 0.06]. Interestingly, for those EGFR wild-type tumors, single-agent EGFR-TKI therapy was inferior to EGFR-TKIs added to chemotherapy in PFS [HR = 0.38 (0.33, 0.44), p < 0.001] and OS [HR = 0.83 (0.71, 0.97), p = 0.02]. Conclusions: For these EGFR mutant patients, single-agent EGFR-TKI therapy prolonged PFS over chemotherapy. However, single-agent EGFR-TKI therapy was inferior to chemotherapy in PFS for those EGFR wild-type patients. Single-agent EGFR-TKI therapy could improve PFS over the combination of EGFR-TKIs and chemotherapy in these EGFR mutant patients. However, EGFR-TKIs combined with chemotherapy could provide additive PFS and OS benefit over single-agent EGFR-TKI therapy in those EGFR wild-type patients.

2386 Association between the peripheral immune status of granulocytic myeloid-derived suppressor cells and progression-free survival chemotherapy

2386 Association between the peripheral immune status of granulocytic myeloid-derived suppressor cells and progression-free survival chemotherapy

PCN23 - Comparison Between Everolimus (Afinitor®) and Chemotherapy Agents (Capecitabine, Docetaxel and Doxorubicin) for the Treatment of Hormone Receptor Positive (HR+) HER2 Negative (HER2–) Advanced or Metastatic Breast Cancer

This study compares everolimus (EVE) versus the most commonly used chemotherapy agents in UK clinical practice (capecitabine [CAPE], docetaxel [DOC] and doxorubicin [DOX]) in patients with hormone receptor positive, HER2 negative advanced or metastatic breast cancer with the purpose of determining the effect of everolimus versus chemotherapy through the derivation of hazard ratios (HR). A systematic review of the literature was performed to find evidence that could link EVE with chemotherapy (CAPE, DOC and DOX) in terms of progression-free survival (PFS) and overall survival (OS). No head-to-head trials comparing EVE versus chemotherapy were found, the only study that linked hormonal therapy with chemotherapy for treatment of metastatic breast cancer was Wilcken et al. (2003). Wilcken et al. identified three studies which compared OS for tamoxifen versus chemotherapy. None of the studies identified in the systematic review reported PFS. The link between EVE versus chemotherapy through Wilcken et al.(2003) was established via tamoxifen (using Bucher methods), so it was assumed that PFS for chemotherapy would be the same as PFS for everolimus versus tamoxifen (TAM) from the TAMRAD trial. HR for everolimus versus tamoxifen for PFS from the TAMRAD trial is 0.54. For OS, Wilcken et al. derived a HR for chemotherapy versus tamoxifen of 0.94. To calculate the HR for OS for everolimus vs tamoxifen the inverse was applied to the OS HR from the TAMRAD trial (0.45), hence (1/0.45)=2.22. The HR for OS for everolimus versus chemotherapy is therefore (0.94x2.22)=2.09. Because a class effect was assumed for the three chemotherapy agents, these HRs were applied to capecitabine, docetaxel and doxorubicin equally. Compared with the most commonly used chemotherapy agents in UK clinical practice (CAPE, DOC and DOX), everolimus has a lower risk of death as demonstrated by the HRs derived.

IS4-11 - Vinorelbine Plus Cisplatin Versus Gefitinib in Resected Non-Small-Cell Lung Cancer Haboring Activating EGFR Mutation (WJOG6410L)

ABSTRACT Background Vinorelbine plus cisplatin after completely resected stage II-III non-small cell lung cancer (NSCLC) is a standard therapy. Stage IV non-small cell lung cancer (NSCLC) harboring mutations in the epidermal growth factor receptor (EGFR) is quite sensitive to tyrosine kinase inhibitors (TKIs). Three randomized trials demonstrated that gefitinib is superior to platinum based chemotherapy in progression free survival. Retrospective analysis of adjuvant TKIs therapy for patient with resected lung cancer harboring EGFR mutation showed favorable trend toward improvement in disease free survival (DFS) and overall survival (OS). (J Thorac Oncol. 2011;6: 569–575) BR19 comparing adjuvant gefitinib versus placebo for completely resected NSCLC without any selection of biomarker was closed early and did not show any benefit of adjuvant gefitinib, even in the EGFR mutation positive cohort. The randomized trial in adjuvant therapy with erlotinib versus placebo for patients with overexpression of EGFR protein has complete enrolment already. We conduct the first randomized phase III trial comparing adjuvant gefitinib with chemotherapy in patients with completely resected stage II-III NSCLC harboring EGFR mutations. Methods Patients who have undergone complete resection and have EGFR mutation, deletions in exon 19, or L858R point mutation at exon 21 and without T790M mutation are randomly assigned gefitinib 250mg a day for 2 years or vinorelbine 25mg/m2 days 1 and 8, plus cisplatin 80mg/m2 day 1, every 3 weeks for 4 courses. The primary end point is DFS and secondary end points are OS and safety. On the basis of previous studies, we assume the hazard ratio of DFS is 0.65. To demonstrate this improvement in DFS, 230 patients in total would be needed during 3-year accrual period. Status Now This trial has begun from September 12 among 22 institutes in Japan. Until now (March 31. 2012), 20 cases have been enrolled.

Vinorelbine plus cisplatin versus gefitinib in resected non-small cell lung cancer haboring activating EGFR mutation (WJOG6410L).

TPS7110 Background: Vinorelbine plus cisplatin after completely resected stage II-III non-small cell lung cancer (NSCLC) is a standard therapy. Stage IV non-small cell lung cancer (NSCLC) harboring mutations in the epidermal growth factor receptor (EGFR) is quite sensitive to tyrosine kinase inhibitors (TKIs). Three randomized trials demonstrated that gefitinib is superior to platinum based chemotherapy in progression free survival. Retrospective analysis of adjuvant TKIs therapy for patient with resected lung cancer harboring EGFR mutation showed favorable trend toward improvement in disease free survival (DFS) and overall survival (OS). (J Thorac Oncol. 2011;6: 569–575) BR19 comparing adjuvant gefitinib vs. placebo for completely resected NSCLC without any selection of biomarker was closed early and did not show any benefit of adjuvant gefitinib, even in the EGFR mutation positive cohort. The randomized trial in adjuvant therapy with erlotinib vs. placebo for patients with overexpression of EGFR protein has complete enrolment already. We conduct the first randomized phase III trial comparing adjuvant gefitinib with chemotherapy in patients with completely resected stage II-III NSCLC harboring EGFR mutations. Methods: Patients who have undergone complete resection and have EGFR mutation, deletions in exon 19, or L858R point mutation at exon 21 and without T790M mutation are randomly assigned gefitinib 250mg a day for 2 years or vinorelbine 25mg/m2 days 1 and 8, plus cisplatin 80mg/m2 day 1, every 3 weeks for 4 courses. The primary endpoint is DFS and secondary endpoints are OS and safety. On the basis of previous studies, we assume the hazard ratio of DFS is 0.65. To demonstrate this improvement in DFS, 230 patients in total would be needed during 3-year accrual period. This trial has begun from September 12 among 22 institutes in Japan. Until now (January 31. 2012), 13 cases have been enrolled. Five cases were enrolled in latest 1 month.

Outcomes and toxicities for the treatment of stage IVB cervical cancer

The prognosis of stage IVB cervical cancer is generally poor. In the current study, treatment outcomes were evaluated in patients with International Federation of Gynecologic Oncology stage IVB cervical cancer treated with radiotherapy and chemotherapy for progression-free survival (PFS) and treated-related toxicities. The medical records of the patients with stage IVB cervical cancer who were treated at the National Cancer Center, South Korea were reviewed retrospectively. From February 2002 to February 2010, 45 patients were diagnosed with FIGO stage IVB cervical cancer. Survival and toxicities were compared between the 13 patients with concomitant chemoradiotherapy (CCRT) with weekly cisplatin versus 20 patients with CCRT with 5-fluorouracil/cisplatin. Initial treatment included weekly cisplatin-CCRT, 5-fluorouracil/cisplatin-CCRT, neoadjuvant chemotherapy, and radiotherapy with subsequent combination chemotherapy in 13, 20, 4, and 5 patients, respectively. Overall survival (OS) and PFS were 26.2 and 6.7 months, respectively. There was no statistical difference in OS (p = 0.47) and PFS (p = 0.64) between the weekly cisplatin-CCRT and 5-fluorouracil/cisplatin-CCRT groups; however, the incidence of anemia >grade 3 as an acute toxicity was higher in the 5-fluorouracil/cisplatin-CCRT chemotherapy regimen group than the weekly cisplatin-CCRT group (p = 0.03). Acute toxicity >grade 2 showed a tendency to be higher in the 5-fluorouracil/cisplatin-CCRT group. Based on multivariate analysis, poor performance status was the only independent prognostic factor of OS (p = 0.03, 9.77; 95% CI 1.3-73.3) and PFS (p = 0.04, 9.58; 95% CI 1.14-81.26). CCRT using combination chemotherapeutic agents may not have survival advantage over single agent cisplatin-based CCRT. Further improvement in treatment is needed to increase survival outcomes and to decrease treatment-related toxicities in patients with stage IVB cervical cancer.

Feasibility and efficacy of second-line chemotherapy at recurrence for pediatric low-grade gliomas: A comparative population-based study

2069 Background: Chemotherapy is widely accepted as the first-line therapy for pediatric low-grade gliomas (PLGG). Treatment modalities for further progression are controversial. Radiation therapy is still widely used, but the role for repeated chemotherapy remains unclear. The aim of the study was to determine treatment outcome for PLGG treated by chemotherapy at recurrence. Methods: The study group consisted of patients who received chemotherapy due to progression after initial chemotherapy protocol. These were compared to patients treated with chemotherapy at diagnosis, patients who received chemotherapy at third progression and to patients who received radiotherapy at recurrence. Results: From 1990–2007, 80 patients received chemotherapy as first-line treatment for PLGG. 36 received chemotherapy as second-line and 11 at further recurrence. 31 patients were treated with radiation at recurrence. There was no gender preference. Median follow-up time was 6.85 yrs. Histology revealed grade 1 astrocytoma in 73%. The most common location was optic pathway with 49%, followed by brainstem and suprasellar (14 %) and thalamic and spinal location (11 %). The most common initial protocol was vincristine and carboplatin (80%). The most common protocol at relapse was vinblastine (87%). Five-year progression-free survival (PFS) for first-line chemotherapy was 49% ± 6 compared to 41 ± 9% with second-line chemotherapy (p=0.2). For further chemotherapy PFS was comparable but so far with shorter follow-up. Five years PFS for the second-line chemotherapy and radiotherapy at recurrence group were 41 ± 9% and 78 ± 5 % respectively (p=0.003). Only 4 patients died, out of whom only 2 due to tumor progression. Conclusions: This is the first study to address the role of chemotherapy for recurrent PLGG. In contrast to other tumours chemotherapy at diagnosis as well as at first recurrence is associated with similar outcome. Nevertheless in this study radiotherapy was superior to chemotherapy. Prospective studies to assess toxicity and long-term outcome are needed. No significant financial relationships to disclose.