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18. 20. ZÁŘÍ 2014 / 18
TH
20
TH
SEPTEMBER 2014 / OLOMOUC
PNEUMOONKOLOGIE I
Sobota 20. 9. 2014 / 11.45–12.45 / Sál Pegasus
PNEUMOONKOLOGIE I
Sobota 20. 9. 2014 / 11.45–12.45 / Sál Pegasus
Adjuvant therapy of completely resected NSCLC:
current status and perspectives
Pirker R.
Department of Medicine I, Medical University of Vienna,
Austria
Approximately 25-30% of patients with non-small cell
lung cancer (NSCLC) are diagnosed with localized disease
and undergo surgery with curative extent. Within phase III
trials, adjuvant chemotherapy increased the survival rates at
5 years by 4 to 15%. The Lung Adjuvant Cisplatin Evaluation
(LACE) meta-analysis, which was based on five cisplatin-based
trials, demonstrated a survival benefit of 5.3% ± 1.6% at 5 years.
Thus adjuvant chemotherapy with a cisplatin-based doublet,
preferentially cisplatin plus vinorelbine, has been established
as a standard treatment for patients with completely resected
NSCLC stages II and III.
Customized chemotherapy has the potential to improve
outcome of adjuvant chemotherapy. Predictive biomarkers
with regard to adjuvant chemotherapy have been characterized
but require prospective validation. Phase III trials comparing
customized chemotherapy based on molecular tumor
parameters with chemotherapy are ongoing.
Targeted therapies are also evaluated in the adjuvant setting.
The NCIC CTG BR19 study, which compared adjuvant gefitinib
with placebo in patients with completely resected NSCLC, failed
to demonstrate differences in overall survival or disease-free
survival between the two treatment arms. The RADIANT phase III
trial compared erlotinibwith placebo in patients with completely
resected EGFR-positive NSCLC with or without adjuvant
chemotherapy. The trial failed to demonstrate an improvement in
disease-free survival. Adjuvant therapy with EGFR tyrosine kinase
inhibitors is currently studied in patients with EGFR mutation-
positive tumors. A trial performed in China (ADJUVANT) compares
the efficacy of adjuvant gefitinibwith adjuvant chemotherapy in
patients with stage II-IIIA EGFR-mutation-positive NSCLC. The trial
plans to enroll 220 patients and has disease-free survival as the
primary endpoint. A similar trial is ongoing in Japan. Bevacizumab
added to adjuvant chemotherapy is currently evaluated in the
North American Intergroup Adjuvant Chemotherapy Trial ECOG
1505 in patients with early-stage NSCLC. In this trial, patients
with stage IB (>4 cm), II or IIIA NSCLC will be randomized to
receive adjuvant cisplatin-based chemotherapy either alone or
in combination with bevacizumab.
Another strategy to improve outcome in the adjuvant
setting focuses on cancer vaccines. An interesting tumor-
specific antigen is MAGE-A3 which can be detected in about
35% of early-stage NSCLC but not in normal cells. Despite
promising phase II data, the phase III trial (MAGRIT) failed to
show an improvement in disease-free survival for the MAGE-A3
vaccine compared to placebo.
Cisplatin or carboplatin in adjuvant
chemotherapy of NSCLC?
Kolek V.
Dept. of Respiratory Medicine, University Hospital,
Palacky University, Olomouc
Adjuvant chemotherapy (AC) of NSCLC is used in stages
IB, II and III. Platinum based doublets are applied, combination
with vinorelbine is a preferable regimen according to the big
trials meta-analysis. A matter of debate can be the number of
cycles, dosage, the acceptable delay after surgery, PS and age of
patients. Results of trials with biologically targeted therapy are
not conclusive yet. AC with cisplatin (CDDP) is considered more
effective than carboplatin (CBDCA), which is recommended in
older and polymorbid patients. Nevertheless there is not a single
head to head study in AC setting and only meta-analyses on
inoperable NSCLC exist. Some reasons support carboplatin usage
in clinical practice, especially lower toxicity and better tolerance.
aim:
Present study is evaluating differences between
CBDCA and CDDP in two multicenter prospective series of
AC in NSCLC. Patients were treated with combination of orally
or intravenously applied vinorelbine with CBDCA or CDDP in
21 day regimens.
methods:
Patients after complete resection with stage IB,
II and IIIA NSCLC (6 th TNM classification), PS 0–1, age of 18 to
75 years were included. In the first series – SWITCH, vinorelbin
25 mg/m
2
was applied on the day one intravenously and on
the day eight 60 mg/m
2
orally. In the second study -FONA,
vinorelbine was applied on days 1 and 8 fully orally (80 mg/
m
2
, in the first cycle 60 mg/m
2
). CDDP in dose of 80 mg/m
2
or
CBDCA (AUC 5) were chosen individually according to center
and patient preference. Differences between results of CBDCA
and CDDP in AC were evaluated in terms of tolerability, dose
intensity and toxic side effects of treatment. Survival was
evaluated only in SWITCH series.
results:
In SWITCH series, 154 pts were included. Out of them
74 (48%) pts (mean age 64 y) with CBDCA and 80 pts (mean age
62 y) with CDDP (52%). In pts treated with CBDCA, there were
higher relative dose delivery (94% vs 90%), mean No of cycles/
patient (3.83 vs 3.76) and total No of applied cycles (283.5 vs
259.5) than in pts treated with CDDP. In FONA series, 214 pts
were included. Out of them 104 (48.5%) pts (mean age 64 y)
with CBDCA and 110 (51.5%) pts (mean age 61 y) with CDDP.
In pts treated with CBDCA, there were higher relative dose
delivery (95.1% vs 79%) and mean No of cycles/patient (3.80 vs
3.77). Total No of applied cycles was 395.5 in CBDCA vs 415 with
