Annual Meeting Proceedings Part 1 - American Society of Clinical ...

472s Lung Cancer—Non-small Cell Local-Regional/Small Cell/Other Thoracic Cancers
7084 General Poster Session (Board #40C), Sat, 1:15 PM-5:15 PM
Outcomes of sarcomatoid malignant pleural mesothelioma, a distinct
clinical entity. Presenting Author: Elisabetta Gattoni, Oncology ASL21,
Casale Monferrato, Italy
Background: Sarcomatoid malignant pleural mesotheliomas (SMPM), accounting
for 10% of MPM, are resistant to chemotherapy (CT) with median
survival in the range of 6 months. Here we report on clinical outcome of a
large series of SMPM patients treated at our Oncological Department,
located in a particularly asbestos-polluted area in Piedmont (Italy).
Methods: Patients consecutively diagnosed, treated and included in our
MesoDB between 1993 and 2010 were considered for this study. Clinical
and pathological data, treatments, response to CT and outcomes were
analyzed for the present study. Diagnosis was always confirmed by the same
expert pathologist. Results: Data of 672 patients were considered for the
analysis. Among these, 53 (8%) were diagnosed with SMPM (17F/36M).
Median age was 67,6 years. Asbestos exposure was occupational certain in
12, possible in 15, domestic in 3 and environmental in 23. The predominant
symptom at diagnosis was thoracic pain in 34 patients (64%),
followed by dyspnea in 16 (30%), fatigue and weight loss in 2 and palpable
mass in 1. The predominant radiological finding at diagnosis was diffuse
pleural thickening in 23 patients (43%), pleural effusion in 14 (26%),
pleural effusion and pleural thickening in 10 (19%), localized mass in 4
(8%), unknown in 2 (4%). Forty-eight patients received first line CT with
the following regimens: carboplatin/cisplatin and pemetrexed in29, pemetrexed
in 8, cisplatin and raltitrexed in 3, cisplatin and gemcitabine in 3,
gemcitabine in 2, doxorubicin based combination in 3 patients. The
median number of cycles was 4. Overall response rate to first line CT was as
follows: 11 SD (21%), 31 PD (58%) and 6 (11%) patients were not
evaluable for response. Median progression free survival was 3.3 (95%CI
2.6-4.1) months. Eleven patients received a second line CT and no
responses or disease stabilization was observed. Median OS was 7.6
months. Conclusions: This large series of SMPM suggests that standard CT
has only negligible impact on the prognosis, underlying a highly unmet
clinical need. SMPM patients should be treated within phase I-II studies
with investigational agents. Research should focus to a deeper knowledge
of tumor biology and to the identification of druggable targets.
7086 General Poster Session (Board #40E), Sat, 1:15 PM-5:15 PM
Phase II study of amrubicin (AMR) combined with carboplatin (CBDCA) for
refractory relapsed small cell lung cancer (SCLC): North Japan Lung Cancer
Group 0802. Presenting Author: Ryota Saito, Tohoku University Hospital,
Sendai, Japan
Background: AMR, a new anthracycline agent, has achieved some promising
results for advanced SCLC both in the first-line and the second-line
setting. However the efficacy of AMR alone against refractory relapsed
SCLC was relatively low in previous studies. This study was conducted to
evaluate the safety and efficacy of the combination of AMR plus CBDCA in
patients with refractory relapsed SCLC. Methods: Patients with advanced
SCLC who relapsed within 90 days after the completion of first-line
chemotherapy received AMR (30 mg/m2 , day1-3) and CBDCA (AUC 4.0,
day 1) every 3 weeks. The primary endpoint of this study was overall
response rate (ORR), and secondary endpoints were progression-free
survival (PFS), overall survival and toxicity profile. Assuming that ORR of
45% in eligible patients would indicate potential usefulness while ORR of
20% would be the lower limit of interest, with alpha � 0.10 and beta �
0.10, at least 24 patients were required. Results: From September 2008 to
May 2011, 30 patients were enrolled from 10 institutions. One patient was
excluded because of ineligible histology. Patient characteristics were:
Male/Female 26/3; median age 67 (range 50-81); Performance status
0/1/2 9/16/4. The median number of treatment cycles were 4 (range 1-7).
The objective responses evaluated by RECIST were: CR 0, PR 10, SD 14,
PD 5. The ORR was 34% and the disease control rate was 83%. Median
PFS was 3.5 months and median survival time was 7.3 months. Grade 3-4
neutropenia was observed in 23 patients (79%) and grade 3-4 thrombocytopenia
was observed in 7 patients (24%). One patient (3%) suffered from
grade 3-4 febrile neutropenia. Other grade 3 non-hematological toxicities
such as infection, interstitial lung disease, hyponatremia, hypoglycemia,
were observed in 7 patients (24%). No treatment related death was
observed. Conclusions: This is the first prospective study of AMR combined
with CBDCA for refractory relapsed SCLC, which was effective and well
tolerated. Further investigation of this treatment is warranted.
7085 General Poster Session (Board #40D), Sat, 1:15 PM-5:15 PM
NGR-hTNF and doxorubicin in relapsed small-cell lung cancer (SCLC).
Presenting Author: Raffaele Cavina, Humanitas Cancer Center, Rozzano,
Italy
Background: By selectively damaging tumor vasculature, NGR-hTNF (asparagine-glycine-arginine
human tumor necrosis factor) is able to improve
intratumoral uptake of doxorubicin (D). A phase I trial selected NGR-hTNF
0.8 �g/m2 /day(d)1 and D 75 mg/m2 /d1 every 3 weeks (q3w) for phase II.
Methods: SCLC pts failing one or more platinum-based regimen received
NGR-hTNF until progressive disease (PD) and D up to 550 mg/m2 . This
phase II trial (n�27 pts) had progression-free survival (PFS) as primary end
point, with tumor response assessed q6w by RECIST, while secondary end
points included adverse events (AEs), disease control rate (DCR), and
overall survival (OS). Results: Among 28 pts enrolled (median age 63 years;
M/F 19/9; PS 0/1-2 13/15; prior lines 1/2-3 20/8), 16 pts had platinumresistant
(R) disease (PD�3 months) and 12 pts platinum-sensitive (S)
disease (PD�3 months). At baseline, median neutrophil to lymphocyte
ratio (NLR) was 4 (range 1-20). A total of 114 cycles were given (range
1-10), with 13 pts (46%) having � 4 cycles and 9 pts (32%) � 6 cycles.
No grade 3/4 AEs related to NGR-hTNF were noted, while grade 1/2 AEs
were transient chills (61%). NGR-hTNF did not apparently increase
D-related AEs. Median PFS was 3.2 months (95% CI 2.6-3.8) and 1-year
OS rate was 34%. Overall, DCR was 55% (95% CI 35-74), comprising 6
partial responses (22%; median duration: 6.3 months) and 9 stable
diseases (33%; median duration: 4.1 months). Mean changes from
baseline in target tumor size after 2, 4, and 6 cycles were -9%, -29%, and
-32%, respectively for R disease and -11%, -20%, and -43%, respectively
for S disease. In pts pretreated with � 2 lines, DCR was 75%, median PFS
was 5.1 months, and 1-year OS rate was 44%. In pts with R or S disease,
DCR were 50% and 58% (p�.72), median PFS were 2.7 and 4.1 months
(p�.07), and 1-year OS rates were 27% and 42% (p�.65), respectively. At
multivariate analyses, PFS was not related to baseline characteristics,
while an improved OS was associated only with a low NLR. The 1-year OS
rate was 48% in pts with NLR � 4 and 10% in pts with NLR � 4(p�.007),
while in pts with NLR � 4, 1-year OS rate was 46% in R disease and 50%
in S disease. Conclusions: This combination is well tolerated and active in
platinum resistant and sensitive SCLC and further development is of
interest.
7087 General Poster Session (Board #40F), Sat, 1:15 PM-5:15 PM
Clinical trial design in small cell lung cancer: Surrogate endpoints and
statistical evolution. Presenting Author: Myles Nickolich, Case Comprehensive
Cancer Center, Cleveland , OH
Background: Small cell lung cancer (SCLC) is a devastating disease for
which little recent therapeutic advance has been achieved. SCLC trial
design and reporting may have an impact on the interpretation of studies
conducted. Furthermore the use of surrogate endpoints in SCLC has not
been explored. Methods: Through examining all phase II and III SCLC trials
published in the Journal of Clinical Oncology (8,471 patients from 66 trials
between 1983-2010), we examined how SCLC trial reporting and design
has evolved, determining if the type I error, power, and sample size
calculations were provided. We assessed primary endpoints for all trials and
sought to discover if response rate (RR) or progression-free survival (PFS)
correlated with overall survival (OS). We analyzed response and survival
outcomes for associations using Pearson correlation coefficient and differences
between data groups by ANOVA followed by Tukey’s multiple
comparison procedure. Results: There were increased reporting trends of
statistical design in power (16.7% in 1986-1996 to 77.8% of trials in
2006-2010 [p�0.001]) and type I error (22.2% in 1986-1996 to 72.2%
in 2006-2010 [p�0.005]). 72.2% of trials published in 1986-1996
failed to report a primary endpoint whereas only 5.56% of trials in
2006-2010 failed to do so (p�0.004). Of phase II trials, primary endpoint
was identified as RR in 65%, OS in 25%, and PFS in 10% (p�0.0001).
There is a strong correlation between RR and both PFS (p�0.013) and OS
(p�0.012) in extensive-stage disease (ED) but not limited-stage disease
(LD) (p�0.978 for PFS, p�0.193 for OS). This correlation is for partial
response rate (pRR) but not complete response rate. RR (p�0.029)
exhibits a negative trend over time with a dramatic and significant decrease
in RR across all studies starting in 2005. A strong positive correlation exists
between PFS and OS for LD (p�0.036) and ED (p�0.058). We found no
change in median overall survival (p�0.383). Conclusions: Over time there
has been improvement in reporting the essential statistical data for proper
interpretation of SCLC trials. No change in survival was seen over the past
28 years. RR should be evaluated as a surrogate endpoint for OS in ED but
not LD. pRR correlates with OS and PFS in both LD and ED.
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