Background
Nivolumab showed improvement in overall survival (OS) in ATTRACTION-2, the first phase 3 study in patients with gastric/gastroesophageal junction (G/GEJ) cancer treated with ≥ 2 ...chemotherapy regimens. The 2-year follow-up results of ATTRACTION-2 are presented herein.
Methods
ATTRACTION-2 was a randomized, double-blind, placebo-controlled, phase 3 trial (49 sites; Japan, South Korea, and Taiwan). The median (min–max) follow-up period was 27.3 (24.1–36.3) months. The primary endpoint was OS. A subanalysis of OS was performed based on best overall response and tumor-programmed death ligand-1 (PD-L1) expression status.
Results
Overall, 493 of 601 screened patients were randomized (2:1) to receive nivolumab (330) or placebo (163). OS (median 95% confidence interval; CI) was significantly longer in the nivolumab group (5.26 4.60–6.37 vs 4.14 3.42–4.86 months in placebo group) at the 2-year follow-up (hazard ratio 95% CI, 0.62 0.51–0.76;
P
< 0.0001). A higher OS rate was observed in the nivolumab vs placebo group at 1 (27.3% vs 11.6%) and 2 years (10.6% vs 3.2%). The OS benefit was observed regardless of tumor PD-L1 expression. Among patients with a complete or partial response (CR or PR) in the nivolumab group, the median OS (95% CI) was 26.6 (21.65—not applicable) months; the OS rates at 1 and 2 years were 87.1% and 61.3%, respectively. No new safety signals were identified.
Conclusions
Nivolumab treatment resulted in clinically meaningful long-term improvements in OS in patients with previously treated G/GEJ cancer. The long-term survival benefit of nivolumab was most evident in patients with a CR or PR.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
ATTRACTION-2 demonstrated that nivolumab improved overall survival (OS) vs placebo in patients with advanced gastric cancer treated with ≥ 2 chemotherapy regimens. However, its long-term ...efficacy and outcome of treatment beyond progression (TBP) with nivolumab have not been clarified.
Methods
The 3-year follow-up data were collected. A subset analysis was performed to explore the efficacy of TBP by assessing postprogression survival (PPS) after the first event of disease progression.
Results
Overall, 493 patients were randomized (2:1) to receive nivolumab (
n
= 330) or placebo (
n
= 163). With a median follow-up of 38.5 (range 36.1–47.5) months, OS of the nivolumab group was significantly longer compared to the placebo group (median 5.3 vs 4.1 months; 3-year survival rate, 5.6% vs 1.9%; hazard ratio HR, 0.62 95% confidence interval (CI) 0.50–0.75,
P
< 0.0001). The median OS of responders (
n
= 32) who achieved complete response or partial response was 26.7 months and the 3-year survival rate was 35.5% in the nivolumab group. Overall, 109 patients in the nivolumab group and 37 patients in the placebo group received TBP. PPS tended to be longer in the nivolumab group vs placebo group (median 5.8 vs 4.5 months; HR 95% CI, 0.69 0.47–1.01,
P
= 0.057). In contrast, PPS was similar between both treatment groups in non-TBP patients (median 2.3 vs 2.2 months; HR 0.90,
P
= 0.42).
Conclusions
Long-term efficacy of nivolumab was confirmed at the 3-year follow-up, and a survival benefit of TBP with nivolumab was suggested. Biomarkers for selecting patients suitable for TBP with nivolumab should be identified in the future.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The oral mammalian target of rapamycin inhibitor everolimus demonstrated promising efficacy in a phase II study of pretreated advanced gastric cancer. This international, double-blind, phase III ...study compared everolimus efficacy and safety with that of best supportive care (BSC) in previously treated advanced gastric cancer.
Patients with advanced gastric cancer that progressed after one or two lines of systemic chemotherapy were randomly assigned to everolimus 10 mg/d (assignment schedule: 2:1) or matching placebo, both given with BSC. Randomization was stratified by previous chemotherapy lines (one v two) and region (Asia v rest of the world ROW). Treatment continued until disease progression or intolerable toxicity. Primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), overall response rate, and safety.
Six hundred fifty-six patients (median age, 62.0 years; 73.6% male) were enrolled. Median OS was 5.4 months with everolimus and 4.3 months with placebo (hazard ratio, 0.90; 95% CI, 0.75 to 1.08; P = .124). Median PFS was 1.7 months and 1.4 months in the everolimus and placebo arms, respectively (hazard ratio, 0.66; 95% CI, 0.56 to 0.78). Common grade 3/4 adverse events included anemia, decreased appetite, and fatigue. The safety profile was similar in patients enrolled in Asia versus ROW.
Compared with BSC, everolimus did not significantly improve overall survival for advanced gastric cancer that progressed after one or two lines of previous systemic chemotherapy. The safety profile observed for everolimus was consistent with that observed for everolimus in other cancers.
Esophageal cancer (EC) remains a public health concern with a high mortality and disease burden worldwide. Esophageal squamous cell carcinoma (ESCC) is a predominant histological subtype of EC that ...has unique etiology, molecular profiles, and clinicopathological features. Although systemic chemotherapy, including cytotoxic agents and immune checkpoint inhibitors, is the main therapeutic option for recurrent or metastatic ESCC patients, the clinical benefits are limited with poor prognosis. Personalized molecular-targeted therapies have been hampered due to the lack of robust treatment efficacy in clinical trials. Therefore, there is an urgent need to develop effective therapeutic strategies. In this review, we summarize the molecular profiles of ESCC based on the findings of pivotal comprehensive molecular analyses, highlighting potent therapeutic targets for establishing future precision medicine for ESCC patients, with the most recent results of clinical trials.
Background
There is growing interest in the clinical significance of intratumoral HER2 heterogeneity. Its prognostic and predictive impacts on trastuzumab efficacy were demonstrated in breast cancer. ...However, its clinical significance in gastric cancer is still unclear.
Methods
Twenty-eight HER2-positive gastric cancer patients who had gastrectomy prior to trastuzumab-based chemotherapy were consecutively enrolled. Intratumoral HER heterogeneity was evaluated using whole-tissue sections by immunohistochemistry. When all tumor cells overexpressed HER2 protein, the tumor was defined as homogeneously HER2 (Homo-HER2)-positive group. The others were defined as heterogeneously HER2 (Hetero-HER2)-positive group.
Results
There was no significant difference in clinicopathological features between the two groups. The median progression-free survival (PFS) and overall survival (OS) in the Homo-HER2-positive group were significantly longer than those in the Hetero-HER2-positive group (PFS; 20.0 months 95% CI 17.8–22.2 vs. 6.0 months 95% CI 2.3–9.7; HR 0.11; 95% CI 0.03–0.41;
p
< 0.001, OS; not reached vs. 14.0 months 95% CI 11.9–16.1; HR 0.18; 95% CI 0.06–0.61;
p
= 0.003). In the multivariate analysis, these associations remained significant both in PFS (HR 0.12; 95% CI 0.03–0.46,
p
= 0.002) and OS (HR 0.21; 95% CI 0.06–0.72,
p
= 0.013). With respect to response rate, no statistical difference was found between two groups. However, deeper tumor shrinkage was obtained in the Homo-HER2-positive group compared with the Hetero-HER2-positive group (
p
= 0.046).
Conclusions
Intratumoral HER2 heterogeneity may have robust clinical impact on trastuzumab efficacy in patients with HER2-positive gastric cancer. These findings should be validated by larger independent cohorts and further molecular correlative analyses are warranted.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Purpose
In the ATTRACTION-2 trial, nivolumab significantly improved the survival of advanced gastric cancer patients. The pretreatment neutrophil-to-lymphocyte ratio (NLR) is prognostic in patients ...receiving immune checkpoint inhibitors (ICIs) to treat various cancers. However, a few reports have explored the relationships between NLR changes during ICI treatment and patient survival. Here, we evaluated factors (including NLR changes in patients on nivolumab monotherapy) prognostic for gastric cancer patients.
Methods
We retrospectively analyzed 98 gastric cancer patients who received nivolumab (3 mg/kg or 240 mg/body bi-weekly) at our institution between December 2014 and September 2018. We evaluated pretreatment data, and those obtained 30 and 60 days after treatment commenced. We explored the prognostic utility of relative NLR changes in terms of the overall survival (OS) of patients on nivolumab monotherapy.
Results
Over a median of 4.9 months of follow-up, 98 gastric cancer patients received a median of four treatment courses. The overall response and disease-control rates were 25% and 52%, respectively. The median OS was 6.4 months (95% confidence interval CI 4.6–9.1). On multivariate analysis, factors poorly prognostic in terms of OS were an ECOG performance status of 0–1, a pretreatment NLR > 3, and an NLR difference ≧ 2 over the 60 days before and after nivolumab administration (∆NLR
60
). Patients with ∆NLR
60
values < 2 survived significantly longer than did those with ∆NLR
60
values ≧ 2 (median OS 9.2 months 95% CI 6.4–11.6 vs. 4.0 months 2.1–4.9;
P
= 0.0002).
Conclusions
Nivolumab monotherapy was efficacious in gastric cancer patients. NLR changes during such therapy may be predictive of outcomes.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
S-1 plus oxaliplatin (SOX) is an established treatment for advanced gastric cancer. S-1 adherence is the key to successful SOX treatment. This study focused on S-1 adherence by evaluating real-world ...adherence to S-1 and investigating factors related to decreased S-1 adherence. This study included cases treated between August 1, 2014 and October 12, 2016 at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research. The S-1 adherence rate per cycle was defined as the number of times a patient took S-1/28. In this study, adherence to S-1 was assessed through pill counts and by asking the patient about the reason for non-adherence at a pharmaceutical outpatient clinic. Univariate and multivariate analyses were performed to investigate factors influencing lower adherence. This analysis included 116 patients evaluated for adherence to S-1 on SOX treatment. The median rate of adherence to S-1 was 92.8% in the first cycle and 90.5% in the seventh cycle. The median relative dose intensity of S-1 was 84.6%. In terms of reasons for nonadherence, patients most commonly cited nausea/vomiting (43.7%), diarrhea (20.8%), missed dose (11.8%), and fever (8.1%). Logistic regression analysis was performed using the most appropriate regression equation, and a significant association was detected with 1 factor, number of combined drugs ≥5 (odds ratio (OR) = 2.50; 95% confidence interval (CI), 1.04–6.03, p = 0.04). Eliminating unnecessary concomitant medications helps maintain proper adherence to S-1 in SOX treatment.
Coronavirus disease 2019 (COVID-19) was declared to be a global pandemic by the World Health Organization on March 11, 2020. On April 7, 2020, a state of emergency was declared in Japan, as had been ...by other nations worldwide. This unprecedented crisis has profound implications for patients undergoing chemotherapy and for practicing healthcare professionals. Various reports have shown data indicating that cancer patients with COVID-19 have high morbidity and mortality rates. In order to reduce the use of medical resources to avoid the risk of COVID-19 infections in both cancer patients and health care providers, oncologists now have to draw the line for cancer treatments by maintaining their efficacy while avoiding severe adverse events. In this article, we outlined the decisions made regarding the practice of gastrointestinal oncology in our institution during the COVID pandemic.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
Adjuvant S-1 monotherapy prolongs the survival of patients with pathological stage II or III gastric cancer undergoing D2 gastrectomy. This therapeutic regimen is standard in Japan. ...Unfortunately, some patients who undergo this treatment suffer from recurrent disease. However, information regarding the timing and site-specific trends of recurrence is insufficient.
Methods
Among 396 patients who underwent D2 gastrectomy followed by adjuvant S-1 monotherapy between 2008 and 2012, 122 experienced a recurrence. We retrospectively determined the timing and sites of recurrence.
Results
The median RFS of the 122 patients was 19.5 months, and their 1-, 3- and 5-year RFS rates were 67.2%, 23.0% and 5.7%, respectively. There were no significant differences in RFS among disease substages. Local recurrence, lymph node involvement and peritoneal and hematogenous metastases were found in 6, 25, 63 and 42 patients, respectively. Approximately 10% of patients presented with contemporaneous sites of recurrence. Local recurrence and lymph node metastasis plateaued 3 years after gastrectomy. Peritoneal and hematogenous metastasis increased within 5 years after surgery. In patients with hematogenous metastasis, the number of liver metastases plateaued but increased in others.
Conclusions
In patients with recurrent disease who underwent D2 gastrectomy followed by adjuvant S-1 monotherapy, 80% of recurrences occur within 3 years after gastrectomy. The timing of recurrence is not significantly different among substages. Although the rates of local recurrence and lymph node and liver metastasis plateau after 3 years, peritoneal and the other hematogenous metastases increase within 5 years.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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