Docetaxel-based chemotherapy is effective in metastatic gastric and gastro-oesophageal junction adenocarcinoma. This study reports on the safety and efficacy of the docetaxel-based triplet FLOT ...(fluorouracil plus leucovorin, oxaliplatin and docetaxel) as a perioperative therapy for patients with locally advanced, resectable tumours.
In this controlled, open-label, phase 2/3 trial, we randomly assigned 716 patients with histologically-confirmed advanced clinical stage cT2 or higher or nodal positive stage (cN+), or both, resectable tumours, with no evidence of distant metastases, via central interactive web-based-response system, to receive either three pre-operative and three postoperative 3-week cycles of 50 mg/m2 epirubicin and 60 mg/m2 cisplatin on day 1 plus either 200 mg/m2 fluorouracil as continuous intravenous infusion or 1250 mg/m2 capecitabine orally on days 1 to 21 (ECF/ECX; control group) or four preoperative and four postoperative 2-week cycles of 50 mg/m2 docetaxel, 85 mg/m2 oxaliplatin, 200 mg/m2 leucovorin and 2600 mg/m2 fluorouracil as 24-h infusion on day 1 (FLOT; experimental group). The primary outcome of the trial was overall survival (superiority) analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01216644.
Between Aug 8, 2010, and Feb 10, 2015, 716 patients were randomly assigned to treatment in 38 German hospitals or with practice-based oncologists. 360 patients were assigned to ECF/ECX and 356 patients to FLOT. Overall survival was increased in the FLOT group compared with the ECF/ECX group (hazard ratio HR 0·77; 95% confidence interval CI; 0.63 to 0·94; median overall survival, 50 months 38·33 to not reached vs 35 months 27·35 to 46·26). The number of patients with related serious adverse events (including those occurring during hospital stay for surgery) was similar in the two groups (96 27% in the ECF/ECX group vs 97 27% in the FLOT group), as was the number of toxic deaths (two <1% in both groups). Hospitalisation for toxicity occurred in 94 patients (26%) in the ECF/ECX group and 89 patients (25%) in the FLOT group.
In locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma, perioperative FLOT improved overall survival compared with perioperative ECF/ECX.
The German Cancer Aid (Deutsche Krebshilfe), Sanofi-Aventis, Chugai, and Stiftung Leben mit Krebs Foundation.
Background
For patients receiving immune checkpoint inhibitors, early detection of immune‐related adverse events (irAEs) is critical for one’s safety. To this end, a smartphone app (SOFIA) was ...developed that featured the assessment of electronic patient‐reported outcomes (ePROs) focusing on irAEs as well as a set of comprehensive supportive information. Its feasibility and preliminary efficacy were evaluated in a randomized controlled trial (RCT).
Methods
Patients who received immune checkpoint inhibition therapy were randomly assigned to an intervention group (IG) or a control group (CG; care as usual). During the 12‐week intervention period, IG patients used SOFIA to report twice weekly ePROs and receive cancer‐ and immunotherapy‐relevant contents. Before a patient’s next clinical visit, the physician in charge was given the ePRO reports. The primary objective was to test the feasibility of SOFIA. Furthermore, the preliminary efficacy of SOFIA for health‐related quality of life (HRQOL), psychosocial outcomes, and medical data was examined. Clinical outcomes were assessed at baseline (T0), post‐intervention (T1), and a 3‐month follow‐up (T2).
Results
Seventy‐one patients were randomized to the IG (n = 34) or the CG (n = 37). SOFIA showed high feasibility and acceptance. At T1, patients in the IG reported significantly better HRQOL and role functioning and less depression, distress, and appetite loss. No significant differences were revealed regarding medical data, the utilization of supportive care services, or survival.
Conclusions
SOFIA showed high feasibility and acceptance and improved HRQOL and psychosocial outcomes. These results suggest further evaluation of efficacy in a large‐scale confirmatory multicenter RCT.
An ehealth intervention (SOFIA) for patients with cancer undergoing immunotherapy with immune checkpoint inhibitors showed high feasibility and acceptance in the clinical routine. Results regarding preliminary efficacy revealed better health‐related quality of life and reduced psychosocial symptoms in the intervention group compared to the control group, which indicates the positive effects of SOFIA, and should be investigated in a confirmatory randomized controlled trial.
Background
The optimal surgical approach for adenocarcinoma directly at the esophagogastric junction (AEG II) is still under debate. This study aims to evaluate the differences between right ...thoracoabdominal esophagectomy (TAE) (Ivor–Lewis operation) and transhiatal extended gastrectomy (THG) for AEG II.
Methods
From a prospective database, 242 patients with AEG II (TAE,
n
= 56; THG,
n
= 186) were included and analyzed according to characteristics and perioperative morbidity and mortality and overall survival (chi-square, Mann–Whitney
U
, log-rank, Cox regression).
Results
Groups were comparable at baseline with exception of age. Patients older than 70 years were more frequently resected by THG (
p
= 0.003). No differences in perioperative morbidity (
p
= 0.197) and mortality (
p
= 0.711) were observed, including anastomotic leakages (
p
= 0.625) and pulmonary complications (
p
= 0.494). There was no significant difference in R0 resection (
p
= 0.719) and number of resected lymph nodes (
p
= 0.202). Overall median survival was 38.4 months. Survival after TAE was significantly longer than after THG (median OS not reached versus 33.6 months,
p
= 0.02). Multivariate analysis revealed pN-category (
p
< 0.001) and type of surgery (
p
= 0.017) as independent prognostic factors. The type of surgery was confirmed as prognostic factor in locally advanced AEG II (cT 3/4 or cN1), but not in cT1/2 and cN0 patients.
Conclusions
Our single-center experience suggests that patients with (locally advanced) AEG II tumors may benefit from TAE compared to THG. For further evaluation, a randomized trial would be necessary.
Perioperative systemic treatment is standard of care for Caucasian patients with locally advanced, resectable gastric adenocarcinoma. The prognostic relevance of the microsatellite instability (MSI) ...status in patients undergoing neoadjuvant chemotherapy followed by resection is unclear. We analyzed the association of the MSI status with histological regression and clinical outcome in patients undergoing neoadjuvant systemic treatment. Tumor tissue from patients undergoing neoadjuvant chemotherapy followed by resection for gastric or gastroesophageal‐junction adenocarcinoma was analyzed for MSI status using a mononucleotide marker panel encompassing the markers BAT25, BAT26, and CAT25. Histological regression, relapse‐free survival and overall survival were calculated and correlated with MSI status. We identified the MSI‐H phenotype in 9 (8.9%) out of 101 analyzed tumors. Though a poor histological response was observed in eight out of nine MSI‐H patients, overall survival was significantly better for patients with MSI‐H compared to MSS tumors (median overall survival not reached vs. 38.6 months, log‐rank test p = 0.014). Among MSI‐H patients, an unexpected long‐term survival after relapse was observed. Our data indicate that the MSI‐H phenotype is a favorable prognostic marker in gastric cancer patients undergoing neoadjuvant treatment. The benefit of perioperative cytotoxic treatment in patients with MSI‐H gastric cancer, however, remains questionable. Future trials should stratify patients according to their MSI status, and novel treatment modalities focusing on MSI‐H tumors should be considered.
What's new?
Recent classification of gastric cancer into four molecular subtypes has paved the way toward better patient stratification for therapy. However, to date, the prognostic impact of microsatellite instability (MSI) status in patients with gastric and gastroesophageal junction adenocarcinoma undergoing neoadjuvant systemic therapy remains unclear. Our study shows that despite a poor histological response, clinical outcome among patients with high‐level MSI (MSI‐H) tumors is significantly superior in comparison to patients with microsatellite‐stable (MSS) tumors. The findings suggest that MSI‐H phenotype is a prognostic marker in gastric cancer patients undergoing neoadjuvant treatment, and that future studies should stratify patients according to their MSI status.
Background
To date there is no evidence that more intensive follow-up after surgery for esophagogastric adenocarcinoma translates into improved survival. This study aimed to evaluate the impact of ...standardized surveillance by a specialized center after resection on survival.
Methods
Data of 587 patients were analyzed who underwent curative surgery for esophagogastric adenocarcinoma in our institution. Based on their postoperative surveillance, patients were assigned to either standardized follow-up (SFU) by the National Center for Tumor Diseases (SFU group) or individual follow-up by other physicians (non-SFU group). Propensity score matching (PSM) was performed to compensate for heterogeneity between groups. Groups were compared regarding clinicopathological findings, recurrence, and impact on survival before and after PSM.
Results
Of 587 patients, 32.7% were in the SFU and 67.3% in the non-SFU group. Recurrence occurred in 39.4% of patients and 92.6% within the first 3 years; 73.6% were treated, and of those 17.1% underwent resection. In recurrent patients overall and post-recurrence survival (OS/PRS) was influenced by diagnostic tools (
p
< 0.05), treatment (
p
≤ 0.001), and resection of recurrence (
p
≤ 0.001). Standardized follow-up significantly improved OS (84.9 vs. 38.4 months,
p
= 0.040) in matched analysis and was an independent positive predictor of OS before and after PSM (
p
= 0.034/0.013, respectively).
Conclusion
After PSM, standardized follow-up by a specialized center significantly improved OS. Cross-sectional imaging and treatment of recurrence were associated with better outcome. Regular follow-up by cross-sectional imaging especially during the first 3 years should be recommended by national guidelines, since early detection might help select patients for treatment of recurrence and even resection in few designated cases.
Based on two benchmark studies perioperative chemotherapy (CTx) has become standard treatment for locally advanced esophagogastric adenocarcinoma (EGA) in Europe. However, only half of the patients ...in both studies actually received postoperative CTx (aCTx). Thus, we evaluated the prognostic impact of preoperative CTx (nCTx) and aCTx combined versus nCTx alone. Furthermore, we aimed to identify subgroups potentially beneficial of aCTx and factors associated with its non-administration.
We retrospectively analyzed 299 consecutive patients with EGA, who underwent complete resection (all M0, R0) after nCTx in our institution and were eligible for aCTx. Patients with and without aCTx were compared regarding clinicopathological data, treatment, morbidity, and long-term prognosis.
129 patients (43.1%) did not receive aCTx. Administration of aCTx did not significantly improve overall (OS) and recurrence free survival (RFS) (median OS: 78.2 months vs. not reached, p = 0.331; RFS: 43.3 vs. 41.1 months, p = 0.118), but was an independent positive predictor of RFS (HR 1.6 95%CI 1.1–2.5, p = 0.024). aCTx improved RFS in non-intestinal tumors (p = 0.023) and patients receiving FLOT regimen (p = 0.038). By logistic regression analysis factors predictive of non-administration of aCTx were older age (>65 years: OR 3.2, p = 0.028), longer hospital stay (15–28 days: OR 2.6, p = 0.001; >28 days: OR 5.2, p < 0.001), and histopathologic non-response (OR 1.9, p = 0.023).
Advanced age, histopathologic non-response, and prolonged convalescence due to postoperative morbidity lead to omission of aCTx. However, this study could not provide evidence to support the beneficial role of aCTx in perioperative chemotherapy regimens for a selected patient collective with EGA and excellent prognosis.
The optimal duration of firstline chemotherapy in metastatic esophagogastric cancer is unknown. In most clinical trials therapy was given until tumour progression or limiting toxicity. Maintenance ...concepts aiming to prolong the duration of response and maintain quality of life have been established in other tumour types but not in esophagogastric cancer. S-1 is an oral fluoropyrimidine with proven efficacy in metastatic esophagogastric cancer.
The Maintenance Teysuno® (S-1) in esophagogastric cancer (MATEO) trial is a multinational, randomized phase II study that explores the role of S-1 maintenance therapy in Her-2 negative, advanced esophagogastric adenocarcinoma. After a 12-week firstline platinum-fluoropyrimidine-based chemotherapy patients without tumour progression are randomized in a 2:1 allocation to receive S-1 alone or continue with the same regimen as during the primary period. The primary endpoint is overall survival. Secondary endpoints include safety and toxicity, progression-free survival and quality of life. Correlative biomarker analyses focus on the identification of a subgroup of patients with a prolonged benefit from S-1 based maintenance therapy.
MATEO will be the first trial to define the role of a S-1 based maintenance therapy in patients having received a platinum-based firstline chemotherapy.
NCT02128243 (date of registration: 29-04-2014).
Pancreatic cancer occurs more frequently in older patients, but these are underrepresented in the phase III clinical studies that established the current treatment standards. This leads to ...uncertainty regarding the treatment of older patients with potentially toxic but active regimens like FOLFIRINOX.
We conducted a retrospective analysis of patients treated according to the FOLFIRINOX protocol at our institution between 2010 and 2014 with a focus on older patients.
Overall survival in our cohort was 10.2 months. Only 43% of patients did not need dose adaptations, but dose reductions did not lead to an inferior survival. We did not find evidence that patients aged 65 years and older deemed fit enough for palliative treatment had more toxicities or a worse outcome than younger patients.
We conclude that treatment with the FOLFIRINOX protocol in patients with pancreatic cancer should not be withhold from patients solely based on their chronological age but rather be based on the patient's performance status and comorbidities.
Abstract Introduction Human epidermal growth factor receptor 2 (HER2) amplification is present in a subgroup of gastroo-esophageal cancers (GCs). HER2 inhibition with trastuzumab has shown to improve ...outcomes in advanced disease. Lapatinib ditosylate (LAP), a dual anti-epidermal growth factor receptor (EGFR) and anti-HER2 tyrosine kinase inhibitor with preclinical activity against GC, has been approved in HER2-positive breast cancer. We aimed to study the activity of LAP in HER2-amplified GC. Materials and methods Patients (pts) with HER2-positive (gene amplification or increased copy numbers based on predefined criteria) advanced GC were randomly allocated 1:1 to receive LAP 1250 mg per day 1–21 plus capecitabine (CAP) 2000 mg/m2 on days 1–14 of a 21-day cycle or LAP 1500 mg monotherapy day 1–21 after having failed on a platinum-based first-line therapy. HER2 status was assessed centrally. The primary end-point was the objective response rate (ORR) as assessed by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). We aimed to include 38 pts per arm to show an interesting response rate of ⩾20% in either of the two arms. Results 37 pts were enrolled (18 to LAP + CAP, 19 to LAP). Pts had received a median of three prior treatment lines. 12 pts in the LAP + CAP group (67%) and 12 pts in the LAP group (63%) had received prior trastuzumab. Only two pts (11.1%; 95% confidence interval (CI): 1.37–34.7), both in the LAP + CAP arm, achieved an objective response. The study was closed prematurely for futility. Median time to progression was 42 (95% CI: 38–61) days in the LAP group and 83 (95% CI: 42–86) days in the LAP + CAP group. Other secondary efficacy end-points (progression-free and overall survival) were comparable in the two treatment groups. Rates of diarrhoea were higher with LAP + CAP (61%; 95% CI: 35–83) compared to 26% (95% CI 9–51) with LAP mono, whereas other adverse events were mostly similar between the groups (18 100% versus 17 90%). Discussion Lapatinib showed insufficient activity in HER2-amplified pretreated advanced GC. The safety profile of LAP or LAP + CAP was as expected with some more toxicity in the combination arm. (ClinicalTrials.gov Identifier, NCT01145404).
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