Adjuvant Chemotherapy For Resected Stage Research Articles

Advances in the treatment of gastric cancer: 2022-2023.

To review 2022-2023 studies in gastric cancer. Important studies report the role of laparoscopic surgery in gastric cancer, the activity of immune checkpoint inhibitors in metastatic, locally advanced and adjuvant therapy in gastric cancer, and the effectiveness of zolbetuximab in claudin 18.2-positive metastatic disease. From the Japanese JLSSG0901 Trial, equivalent survival was reported for laparoscopically assisted versus conventional open gastrectomy. Adding nivolumab to adjuvant chemotherapy in resected stage III gastric cancer failed to improve 3-year disease-free survival over chemotherapy alone. Ipilimumab and nivolumab as preoperative therapy in MSI-high gastric cancer resulted in a high rate of pathologic complete response. Trastuzumab added to chemoradiotherapy and surgery in HER2-positive locally advanced esophageal and gastroesophageal junction adenocarcinoma did not improve overall survival over chemoradiotherapy and surgery alone. Adding pembrolizumab to trastuzumab/chemotherapy in metastatic HER2-positive gastric cancer improved antitumor response rate. Addition of zolbetuximab, an antibody targeting claudin 18.2, to first-line chemotherapy in metastatic claudin 18.2-positive gastric cancer improved overall survival. Immune checkpoint inhibition has a role in locally advanced MSI-high and metastatic gastric cancer. Laparoscopic gastrectomy is acceptable in gastric cancer. Zolbetuximab in metastatic gastric cancer will emerge as a new therapy option.

SP2.10 Meta-analysis of adjuvant chemotherapy versus no adjuvant chemotherapy for resected stage I pancreatic cancer

Abstract Aims To evaluate comparative outcomes of pancreatic cancer resection with or without adjuvant chemotherapy in patients with stage I pancreatic cancer. Methods A systematic search of MEDLINE, CENTRAL and Web of Science and bibliographic reference lists were conducted. All comparative studies reporting outcomes of pancreatic cancer resection for stage I cancer with or without adjuvant chemotherapy were included and their risk of bias were assessed using ROBINS-I tool. Survival outcomes were analysed using hazard ratio (HR) and odds ratio (OR) for the time-to-event and dichotomous outcomes, respectively. Results We included 5 comparative studies reporting a total of 4,037 patients with resected stage 1 pancreatic cancer of whom 2,374 patients had no adjuvant chemotherapy and the remaining 1663 patients received adjuvant chemotherapy. The use of adjuvant chemotherapy was associated with significantly higher overall survival rate (HR 0.73, 95% CI 0.63-0.84, p<0.00001) compared to no use of adjuvant chemotherapy. However, there was no statistically significant difference in 1-year (81.9% versus 87.4%, OR 0.51, 95% CI 0.14-1.81, p=0.30), 2-year (60.9% versus 67.5%, OR 0.88, 95% CI 0.75-1.03, p=0.10), 3-year (51.8% versus 54.3%, OR 0.99, 95% CI 0.79-1.24, p=0.93), or 5-year survival (27.4% versus 27.5%, OR 1.11, 95% CI 0.95-1.30, p=0.19) between two groups. Conclusions Meta-analysis of best available evidence (level 2a) demonstrates that adjuvant chemotherapy following resected stage I pancreatic cancer seems to improve overall survival compared to no use of adjuvant chemotherapy. Randomised controlled trials are required to escalate the level of evidence and confirm these findings.

Survival benefit with adjuvant chemotherapy in stage III microsatellite-high/deficient mismatch repair colon cancer: a systematic review and meta-analysis

Clinical observations have demonstrated that microsatellite instability-high (MSI-H) and/or deficient MMR (dMMR) status are associated with favorable prognosis and no benefit from 5-Fluorouracil (5-FU)-based adjuvant chemotherapy in patients with resected stage II colorectal cancer (CRC). This study represents a systematic review and meta-analysis exploring the predictive role of MSI-H status in stage III CRC undergoing or not adjuvant chemotherapy. Published articles that evaluated the role of adjuvant chemotherapy in resected stage III CRC from inception to September 2020 were identified by searching the PubMed, EMBASE, and Cochrane Library databases. The random-effects model was conducted to estimate the pooled effect size of OS and DFS. The primary outcome of interest was OS. 21,590 patients with MSI-H/dMMR stage III CRC, from n = 17 retrospective studies, were analyzed. Overall, OS was improved with any adjuvant chemotherapy vs. any control arm (single-agent 5-FU or surgery alone): HR 0.42, 95% CI 0.26–0.66; P < 0.01. Conversely, DFS was not significantly improved (HR 0.7, 95% CI 0.45–1.09; P = 0.11). In patients with stage III MSI-H/dMMR CRC, adjuvant chemotherapy is associated with a significant OS improvement. Thus, MSI-H/dMMR status does represent a predictive factor for postoperative chemotherapy benefit in stage III CRC beyond its prognostic role.

94P - NORTH/HGCSG1003: North Japan multicenter phase II study of oxaliplatin-containing regimen as adjuvant chemotherapy for stage III colon cancer: Final analysis

BackgroundFOLFOX and CAPOX are standard adjuvant chemotherapy for resected stage III colon cancer. MOSAIC and XELOXA trials were performed outside of Japan, thus, we conducted a phase II study (NORTH/HGCSG1003) to assess the efficacy and safety of FOLFOX as adjuvant chemotherapy for Japanese patients(pts) with resected stage III colon cancer (UMIN ID: 000004590). MethodsThis phase II study enrolled patients with resected stage III colon cancer. Patients received 12 cycles of FOLFOX4 or mFOLFOX6. Sample size was determined to be 243 pts. Primary endpoint was disease-free survival (DFS). We assumed an expected 3-year DFS rate of 81.2% in this study. Secondary endpoints included overall survival (OS) and safety. In this meeting, we present for the 5-year OS rate. ResultsFrom Sep 2010 to Mar 2013, 273 pts were enrolled at 28 institutions. Full analysis included 265 patients who received FOLFOX. Patients characteristics were as follows: median age; 65(33-84), Male/female; 131/134, PS 0/1; 258/7, stage IIIA/IIIB/IIIC; 37/197/31, colon/rectosigmoid: 214/51. The most common grade 3-4 adverse events were neutrophil count decreased (48.1%), peripheral sensory neuropathy (6.4%), platelet count decreased (2.3%), and allergic reaction (1.5%). The median number of cycles of FOLFOX was 12, and the completion treatment rate was 80.4%. There was no treatment-related death. The 3-year/5-year DFS rate was 76.0%(95%C.I. 70.3- 80.7)/70.6%(95%C.I. 64.7-75.7). The 3-year/5-year 0S rate was 95.8%(95%C.I. 92.5- 97.7)/88.1%(95%C.I. 83.5-91.5). ConclusionsIn Japanese patients with resected stage III colon cancer, FOLFOX is a well-tolerable regimen as adjuvant chemotherapy. In this trial, the 3-year DFS rate of primary endpoint was not meet the expectation. However, the 3-year DFS and 5-year OS rate in this trial were similar to several pivotal trials. Clinical trial identificationUMIN ID: 000004590. Legal entity responsible for the studyNon-Political Organization: Hokkaido Gastrointestinal Cancer Study Group. FundingNon-Political Organization: Hokkaido Gastrointestinal Cancer Study Group. DisclosureS. Yuki: Honoraria (self): Yakult Honsha Co. Ltd. All other authors have declared no conflicts of interest.

Gut microbiome associated with chemotherapy-induced diarrhea from the CapeOX regimen as adjuvant chemotherapy in resected stage III colorectal cancer

BackgroundChemotherapy induced diarrhea (CID) is a common side effect in patients receiving chemotherapy for cancer. The aim of our study was to explore the association between gut microorganisms and CID from the CapeOX regimen in resected stage III colorectal cancer (CRC) patients.ResultsAfter screening and identification, 17 stool samples were collected from resected stage III CRC patients undergoing the CapeOX regimen. Bacterial 16S ribosomal RNA genes was sequenced, and a bioinformatics analysis was executed to screen for the distinctive gut microbiome and the functional metabolism associated with CID due to the CapeOX regimen. The gut microbial community richness and community diversity were lower in CID (p < 0.05 vs control group). Klebsiella pneumoniae was the most predominant species (31.22%) among the gut microbiome in CRC patients with CID. There were 75 microorganisms with statistically significant differences at the species level between the CRC patients with and without CID (LDA, linear discriminant analysis score > 2), and there were 23 pathways that the differential microorganisms might be involved in.ConclusionsThe gut microbial community structure and diversity have changed in CRC patients with CID. It may provide novel insights into the prevention and treatment of CID.

Gemcitabine-cisplatin (GC) as adjuvant chemotherapy in resected stage II and stage III gallbladder cancers (GBC): a potential way forward.

Data on adjuvant chemotherapy with gemcitabine-cisplatin (GC) in resected gallbladder cancers (GBC) are scarce. Patients who underwent upfront curative resection for GBC from 2010 to 2016 were analyzed. Patients with stage II-III GBC treated with adjuvant GC were analyzed. A total of 242 patients were evaluated, of whom 125 patients received GC regimen as adjuvant chemotherapy. The median age was 50years (range 31-74), majority were female (77.6%), and 37 patients (29.6%) had raised CA 19.9 levels at baseline. One hundred and thirteen patients (90.4%) underwent radical cholecystectomy with R0 resections. Median number of GC administered was 6, with completion rates of 84%. Toxicity data were comprehensively available for 110 patients, with common grade 3 and grade 4 being neutropenia (9.9%), fatigue (7.3%) and febrile neutropenia (3.6%), respectively. With a median follow-up of 36.88months, 3-year RFS was 60.3%. Patients with stage II (28%; n = 35), stage IIIA (28%; n = 35) and stage IIIB GBC (44%; n = 55) had a 3-year OS of 91.9, 67 and 58.1% (p = 0.001), respectively. Patients with stage II-III GBC undergoing R0 resections receiving adjuvant GC have good tolerance, high completion rates and encouraging outcomes in a non-trial high GBC prevalence scenario.

North Japan multicenter phase II study of oxaliplatin-containing regimen as adjuvant chemotherapy for stage III colon cancer (NORTH/HGCSG1003).

807 Background: FOLFOX and XELOX are standard adjuvant chemotherapy for resected stage III colon cancer. MOSAIC and XELOXA trials were performed outside of Japan, thus, we conducted a phase II study (NORTH/HGCSG1003) to assess the efficacy and safety of FOLFOX as adjuvant chemotherapy for Japanese patients(pts) with resected stage III colon cancer (UMIN ID: 000004590). Methods: This phase II study enrolled patients with resected stage III colon cancer. Patients received 12 cycles of FOLFOX4 or mFOLFOX6. Sample size was determined to be 243 pts. Primary endpoint was disease-free survival (DFS). We assumed an expected 3-year DFS rate of 81.2% in this study. Secondary endpoints included overall survival (OS) and safety. In this meeting, we present for the 3-year DFS rate. Results: From Sep 2010 to Mar 2013, 273 pts were enrolled at 28 institutions. Full analysis included 265 patients who received FOLFOX. Patients characteristics were as follows: median age ; 65(33-84), Male/female ; 131/134, PS 0/1 ; 258/7, stage IIIA/IIIB/IIIC ; 37/197/31, colon/rectosigmoid: 214/51. The most common grade 3-4 adverse events were neutrophil count decreased (48.1%), peripheral sensory neuropathy (6.4%), platelet count decreased (2.3%), and allergic reaction (1.5%). The median number of cycles of FOLFOX was 12, and the completion treatment rate was 80.4%. There was no treatment-related death. The 3-year DFS rate was 75.2 percent (95% confidence interval, 69.6 to 80.0). Conclusions: In Japanese patients with stage III colon cancer, FOLFOX is a well-tolerable regimen as adjuvant chemotherapy. In this trial, the 3-year DFS rate of primary endpoint was not meet the expectation (81.2%). However, the 3-year DFS rate in this trial was similar to several pivotal trials. We plan to do subset analysis. Clinical trial information: UMIN000004590.

Adjuvant Chemotherapy in Resected Stage II Non-small Cell Lung Cancer: Evaluating the Impact of Dose Intensity and Time to Treatment

AimsPlatinum-based adjuvant chemotherapy is the standard of care for resected stage II non-small cell lung cancer (NSCLC). The purpose of this population-based study was to identify factors that predict for receiving adjuvant therapy and to assess the effect of delayed administration and dose reduction on survival. Materials and methodsThe British Columbia Cancer Agency provides cancer care to 4.6 million individuals across a large and varied geographical area. A retrospective review was conducted of all referred patients with resected stage II NSCLC between 2005 and 2010. Baseline characteristics, systemic therapy details and outcomes were recorded. ResultsOf 258 stage II NSCLC patients, 158 received adjuvant chemotherapy (61%). No-adjuvant versus adjuvant population: men 52%/57%, median age 67/62, Eastern Cooperative Oncology Group (ECOG) ≤ 1 55%/75%, Charlson comorbidity score (CCS) ≤ 1 61%/74%, pneumonectomy 11%/26%. In patients who received chemotherapy, treatment details were: cisplatin/carboplatin based 81%/19%, median cycles delivered 4, median time from surgery to adjuvant chemotherapy 8 weeks, 72% received ≥ 80% (cisplatin < 256 mg/m2 and carboplatin < AUC 19.2) total planned dose. On multivariate analysis younger age, better ECOG and pneumonectomy were predictive of adjuvant treatment. Overall survival of adjuvant-treated patients was inferior for those with CCS ≥ 2, age ≥ 70 and reduced dose intensity on multivariate analysis. The surgery to chemotherapy interval did not affect overall survival. ConclusionsPneumonectomy and factors associated with better functional status predicted for receiving adjuvant chemotherapy. For patients who received adjuvant chemotherapy the total platinum dose given affected survival but time from surgery did not. A higher platinum dose delivery was important in maintaining the efficacy of adjuvant chemotherapy for resected stage II NSCLC in this retrospective population-based study.

Safety analysis of FOLFOX as adjuvant chemotherapy for stage III colon cancer in phase II study (NORTH/HGCSG1003): Detailed analysis of peripheral sensory neuropathy.

701 Background: Oxaliplatin-containing regimen is a standard adjuvant chemotherapy for resected stage III colon cancer. Oxaliplatin-containing regimens were investigated for their efficacy in patients with resected stage III colon cancer in MOSAIC and XELOXA studies. Since these two international randomized studies were performed outside of Japan, we conducted a phase II study (NORTH/HGCSG1003) to assess the efficacy and safety of FOLFOX as adjuvant chemotherapy in Japanese patients (pts) with resected stage III colon cancer (UMIN ID: 000004590). Methods: This phase II study enrolled patients with resected stage III colon cancer. Patients received 12 biweekly cycles of FOLFOX4 or mFOLFOX6. Sample size was determined to be 243 pts. Primary endpoint was DFS. Secondary endpoints included overall survival (OS) and safety. Results: From September 2010 to March 2013, 273 pts were enrolled at 28 institutions. Safety analysis included 265 patients who received FOLFOX. Patients characteristics were as follows: median age, 65 (33-84); male/female: 131/134; PS 0/1:258/7; stage IIIA/IIIB/IIIC: 37/197/31; colon/rectosigmoid: 214/51. The most common grade 3-4 adverse events were neutrophil count decreased (48.1%), platelet count decreased (2.3%), and allergic reaction (1.5%). The incidence of peripheral sensory neuropathy (PSN) was 41.9% (grade 1), 38.1% (grade 2), and 6.4% (grade 3). PSN tended to be serious depending on the cumulative dose of oxaliplatin (table 1). Median cumulative dose of oxaliplatin at which PSN occurred were as follows: grade 1; 170 mg/m2, ≥ grade 2; 850 mg/m2, ≥ grade 3; (-). The median number of cycles of chemotherapy was 12, and the completion treatment rate was 80.4%. There was no treatment-related death. Conclusions: In Japanese patients with stage III colon cancer, FOLFOX is a well-tolerable regimen as adjuvant chemotherapy. Clinical trial information: 000004590. [Table: see text]

Bevacizumab plus oxaliplatin-based chemotherapy as adjuvant treatment for colon cancer (AVANT): a phase 3 randomised controlled trial

Bevacizumab improves the efficacy of oxaliplatin-based chemotherapy in metastatic colorectal cancer. Our aim was to assess the use of bevacizumab in combination with oxaliplatin-based chemotherapy in the adjuvant treatment of patients with resected stage III or high-risk stage II colon carcinoma. Patients from 330 centres in 34 countries were enrolled into this phase 3, open-label randomised trial. Patients with curatively resected stage III or high-risk stage II colon carcinoma were randomly assigned (1:1:1) to receive FOLFOX4 (oxaliplatin 85 mg/m(2), leucovorin 200 mg/m(2), and fluorouracil 400 mg/m(2) bolus plus 600 mg/m(2) 22-h continuous infusion on day 1; leucovorin 200 mg/m(2) plus fluorouracil 400 mg/m(2) bolus plus 600 mg/m(2) 22-h continuous infusion on day 2) every 2 weeks for 12 cycles; bevacizumab 5 mg/kg plus FOLFOX4 (every 2 weeks for 12 cycles) followed by bevacizumab monotherapy 7·5 mg/kg every 3 weeks (eight cycles over 24 weeks); or bevacizumab 7·5 mg/kg plus XELOX (oxaliplatin 130 mg/m(2) on day 1 every 2 weeks plus oral capecitabine 1000 mg/m(2) twice daily on days 1-15) every 3 weeks for eight cycles followed by bevacizumab monotherapy 7·5 mg/kg every 3 weeks (eight cycles over 24 weeks). Block randomisation was done with a central interactive computerised system, stratified by geographic region and disease stage. Surgery with curative intent occurred 4-8 weeks before randomisation. The primary endpoint was disease-free survival, analysed for all randomised patients with stage III disease. This study is registered with ClinicalTrials.gov, number NCT00112918. Of the total intention-to-treat population (n=3451), 2867 patients had stage III disease, of whom 955 were randomly assigned to receive FOLFOX4, 960 to receive bevacizumab-FOLFOX4, and 952 to receive bevacizumab-XELOX. After a median follow-up of 48 months (range 0-66 months), 237 patients (25%) in the FOLFOX4 group, 280 (29%) in the bevacizumab-FOLFOX4 group, and 253 (27%) in the bevacizumab-XELOX group had relapsed, developed a new colon cancer, or died. The disease-free survival hazard ratio for bevacizumab-FOLFOX4 versus FOLFOX4 was 1·17 (95% CI 0·98-1·39; p=0·07), and for bevacizumab-XELOX versus FOLFOX4 was 1·07 (0·90-1·28; p=0·44). After a minimum follow-up of 60 months, the overall survival hazard ratio for bevacizumab-FOLFOX4 versus FOLFOX4 was 1·27 (1·03-1·57; p=0·02), and for bevacizumab-XELOX versus FOLFOX4 was 1·15 (0·93-1·42; p=0·21). The 573 patients with high-risk stage II cancer were included in the safety analysis. The most common grade 3-5 adverse events were neutropenia (FOLFOX4: 477 [42%] of 1126 patients, bevacizumab-FOLFOX4: 416 [36%] of 1145 patients, and bevacizumab-XELOX: 74 [7%] of 1135 patients), diarrhoea (110 [10%], 135 [12%], and 181 [16%], respectively), and hypertension (12 [1%], 122 [11%], and 116 [10%], respectively). Serious adverse events were more common in the bevacizumab groups (bevacizumab-FOLFOX4: 297 [26%]; bevacizumab-XELOX: 284 [25%]) than in the FOLFOX4 group (226 [20%]). Treatment-related deaths were reported in one patient receiving FOLFOX4, two receiving bevacizumab-FOLFOX4, and five receiving bevacizumab-XELOX. Bevacizumab does not prolong disease-free survival when added to adjuvant chemotherapy in resected stage III colon cancer. Overall survival data suggest a potential detrimental effect with bevacizumab plus oxaliplatin-based adjuvant therapy in these patients. On the basis of these and other data, we do not recommend the use of bevacizumab in the adjuvant treatment of patients with curatively resected stage III colon cancer. Genentech, Roche, and Chugai.

Multimodale Therapie des kolorektalen Karzinoms

Adjuvant chemotherapy for resected stage III colon cancer is indicated for all patients, including elderly patients >70years. In general, adjuvant oxaliplatin-fluoropyrimidine chemotherapy should be started within 6weeks after tumor resection and should be given for a period of 6months. However, patients aged >70 should receive fluoropyrimidine mono-chemotherapy. This mono-therapy, but not an oxaliplatin-based combination, can also be considered for patients with standard risk stage II tumors without microsatellite instability. In stage II patients with a high risk constellation adjuvant oxaliplatin-fluoropyrimidine combination therapy should be considered. Patients with stage II and III rectal cancer require neoadjuvant radiochemotherapy with fluoropyrimidine followed by adjuvant fluoropyrimidine treatment. There is no role for the use of VEGF- or EGFR-antibodies in the adjuvant therapy of colon cancer or in neoadjuvant therapy of rectal cancer. The prognosis of patients with primary resectable colorectal liver metastases may be improved by adjuvant or perioperative chemotherapy, while neoadjuvant systemic chemotherapy frequently facilitates potential curative resection of initially non-resectable liver metastases.

Adjuvant chemotherapy for resected stage II and III colon cancer: Comparison of widely used two prognostic calculators

e15031 Background: Two web based prognostic calculators, Adjuvant! and Numeracy (JCO 22:1797–1806, 2004) are widely used to provide individual patient outcome predictions to aid decisions regarding adjuvant therapy for colon cancer. The comparability of these tools has not been studied yet. The aim of this project was to assess whether the Numeracy and Adjuvant! Colon cancer prognostic tools produced similar results for patients with resected stage II and III colon cancer based on a set of hypothetical patients. Methods: All possible hypothetical scenarios were formulated for the Numeracy calculator based on all potential combinations of age, lymph nodes status, tumor stage, and grade of tumor. These were applied to three post- surgical therapy choices: observation, 5-FU (5-fluorouracil), or FOLFOX (5-FU, leucovorin and oxaliplatin). Predictions for these hypothetical scenarios (N= 192 for males and 192 for females) were also entered into the Adjuvant! Program. Predicted relapse free survival (RFS) and overall survival (OS) were obtained using both calculators. Wilcoxon signed rank tests were used to compare the numerical predictions between the calculators for each outcome. Results: In the majority of the 384 hypothetical patient scenarios, predictions for RFS and OS from Adjuvant! were statistically significantly higher than from Numeracy (p value &lt; 0.05), except for age≥70 for FOLFOX, and the number of positive nodes of 0 and 1–4 using FOLFOX, among males. The net estimate of benefit for RFS and OS for 5-FU over surgery, obtained from Adjuvant! and Numeracy, were similar (for both males and females), but the benefit in RFS and OS for FOLFOX over 5-FU obtained from Adjuvant! was significantly lower than the estimate obtained from Numeracy (p value &lt; 0.05). Conclusions: Based on a hypothetical set of patients with resected stage II and III colon cancer, the estimated benefit in RFS and OS of FOLFOX over 5-FU based chemotherapy is lower in Adjuvant! than in the Numeracy tool (but benefit for 5-FU over surgery alone is similar). Further studies are needed to clarify the discrepancy and to assess which of these tools most accurately reflects actual patient outcome. No significant financial relationships to disclose.

Adjuvant chemotherapy for early-stage non-small cell lung cancer: the past, the present and the future

Complete resection is mandatory in order to achieve a cure in patients with early-stage non-small cell lung cancer (NSCLC). However, despite complete resection, a substantial proportion of patients have disease recurrence, with distant metastases being the primary sites of failure. Recent trials have conclusively demonstrated the benefit of platinum-based adjuvant therapy in patients with resected stage IB and II NSCLC. The role of adjuvant chemotherapy in resected stage III NSCLC is less clear, with trials showing conflicting results. The role of targeted agents in this setting is being investigated. Gene expression profiling studies should help direct chemotherapy to those who would actually benefit from it, thereby saving others from unnecessary toxicity.