www.hpboardreview.com Hematology-Oncology Volume 12, Part 2 39
Neoadjuvant and Adjuvant Therapy for Gastric Cancer
Adjuvant Chemotherapy
Data supporting the use of adjuvant chemotherapy alone is largely derived from trials
done in Asia, typically after a D2 lymph node
dissection, and thus adjuvant chemotherapy has
become the standard of care in that region.
In the Japanese Adjuvant Chemotherapy Trial
of S- 1 for Gastric Cancer (ACTS-GC), a total
of 1059 patients with stage II or III gastric
cancer who had undergone surgery with a
D2 lymphadenectomy were randomly assigned
to 1 year of S- 1 (an oral fluoropyrimidine)
or surgery alone.50 The 5-year overall survival
rate was 72% in the S- 1 group and 61% in the
surgery-only group (HR 0.669 [95% CI 0.54
to 0.83]).51 The 5-year relapse-free survival was
65% in the S- 1 group and 53% in the surgery-only group (HR 0.65 [95% CI 0.537 to 0.793]).
Of note, both arms of the ACTS-GC trial had
significantly higher 5-year overall survival rates
compared to the INT-0116 and MAGIC trials:
43% versus 28% and 36% versus 23% for the
treatment and control groups, respectively. 42,45
Consequently, it is unclear if the benefit of adjuvant chemotherapy can be translated to Western
countries.
The Korean Capecitabine and Oxaliplatin
Adjuvant Study in Stomach Cancer (CLASSIC)
trial published in 2012 also established the role
of adjuvant chemotherapy after D2 gastrectomy.52 A total of 1035 patients with stage II-IIIB
gastric cancer who had curative D2 gastrectomy
were randomly assigned to 8 cycles of adjuvant
XELOX (capecitabine 1000 mg/m2 twice daily
on days 1–14 plus oxaliplatin 130 mg/m2 on day
1, 21-day cycle) or surgery alone. Median follow-up was 34 months in both arms and 67% of patients in the chemotherapy arm completed all 8
cycles of planned chemotherapy. The 3-year DFS
was 74% in the chemotherapy group and 59%
in the surgery-only group (HR 0.56 [95% CI
0.44 to 0.72], P < 0.0001). There was a trend toward improvement in overall survival (83% versus 78%, HR 0.72 [95% CI 0.52 to 1.00]). After
5 years of follow-up, the improvement in overall
survival became statistically significant (78%
versus 69%, HR 0.66 [95% CI 0.51 to 0.85]).53
The benefit of adjuvant chemotherapy was
reinforced by a 2010 meta-analysis comparing
adjuvant chemotherapy to surgery alone in patients with resected gastric cancer.54 A total of
17 randomized controlled trials were included.
Adjuvant fluorouracil-based chemotherapy was
associated with a statistically significant improved
overall survival (HR 0.82 [95% CI 0.76 to 0.90],
P < 0.001) and DFS (HR 0.82 [95% CI 0.75 to
0.90], P < 0.001). Five-year overall survival increased from 49.6% to 55.3% with chemotherapy.
SELECTION OF TREATMENT APPROACH
Since data exists for all 3 approaches (
perioperative chemotherapy, adjuvant chemoradiotherapy, and adjuvant chemotherapy), various
meta-analyses have been done to clarify which
approach is the best. In a recent meta-analysis of
6 randomized controlled trials reported between
2010 and 2012, which involved 1171 patients
with resected gastric cancer, adjuvant chemotherapy was compared to adjuvant chemoradiotherapy.55 Five of the studies were from East
Asia, while one was from a Western country.
Adjuvant chemoradiation was associated with a
lower local-regional recurrence rate (OR 0.46
[95% CI 0.32 to 0.67]) and better 5-year DFS
rate (OR 1.56 [95% CI 1.09 to 2. 24]). However, there was no statistical difference in 5-year
overall survival rate (OR 1. 32 [95% CI 0.92 to
1.88]). Similar results were reported by Zhou
et al in 2016.56 This meta-analysis included 4
randomized controlled trials reported between
2010 and 2015, with a total of 960 patients
who had undergone a D2 resection for gastric
cancer. Compared to adjuvant chemotherapy,
adjuvant chemoradiotherapy significantly reduced the loco-regional recurrence rate (LRRR;
relative risk [RR] 0.50 [95% CI 0.34 to 0.74],
P = 0.0005) and improved DFS (HR 0.73 [95%
CI 0.60 to 0.89], P = 0.002). Again, no difference in overall survival was seen (HR 0.91 [95%
CI 0.74 to 1. 11], P = 0.34).
