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L. Crino
Moderator of
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O16 - NSCLC - Targeted Therapies III (ID 115)
- Event: WCLC 2013
- Type: Oral Abstract Session
- Track: Medical Oncology
- Presentations: 8
- Moderators:H.A. Wakelee, L. Crino
- Coordinates: 10/29/2013, 10:30 - 12:00, Parkside Auditorium, Level 1
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O16.01 - Impact of tumor burden on the overall survival analysis of the LUME-Lung 1 study: a randomized, double-blind phase 3 trial of nintedanib (BIBF 1120) + docetaxel in NSCLC patients progressing after first-line chemotherapy (ID 3284)
10:30 - 12:00 | Author(s): M. Reck, S. Novello, A. Mellemgaard, S. Orlov, R. Kaiser, J. Barrueco, B. Gaschler-Markefski, J. Douillard
- Abstract
- Presentation
Background
Nintedanib is an orally available potent anti-angiogenic agent inhibiting the isoforms of VEGFR, PDGFR and FGFR. LUME-Lung 1 is a placebo-controlled phase 3 trial of nintedanib + docetaxel in second-line NSCLC patients.Methods
Patients with stage IIIB/IV or recurrent NSCLC after failure of first-line chemotherapy were stratified by histology, ECOG PS, prior bevacizumab and brain metastases, and were randomised to nintedanib 200 mg bid + docetaxel 75 mg/m[2] q21d (n=655), or placebo + docetaxel (n=659). The primary endpoint was centrally reviewed PFS after 714 events. The key secondary endpoint was OS after 1,121 events. Predefined sensitivity analyses used baseline sum of longest diameters of target lesions (SLD) and stratification factors, as covariates in the Cox model.Results
The study met its primary endpoint demonstrating a statistically significant improvement in PFS that translated into a 21% reduction in the risk of progression in patients treated with the combination of nintedanib + docetaxel vs placebo + docetaxel (HR 0.79; CI: 0.68, 0.92; p=0.0019; median 3.4 vs 2.7 months), regardless of histology (adenocarcinoma HR 0.77, CI: 0.62, 0.96; p=0.0193; squamous HR 0.77, CI: 0.62, 0.96; p=0.0200). OS was significantly prolonged in adenocarcinoma patients treated with the combination of nintedanib + docetaxel vs placebo + docetaxel (HR 0.83; CI: 0.70, 0.99; p=0.0359; median 12.6 vs 10.3 months) but not in squamous cell carcinoma patients (HR 1.01; CI: 0.85, 1.21; p=0.8908; median 8.6 vs 8.7 months). The intent-to-treat (ITT) analysis of OS in all study patients showed a 1-month improvement that did not reach statistical significance (HR 0.94; CI 0.83, 1.05; p=0.272; median 10.1 vs 9.1 months). When adjusted for SLD, however, a significant OS benefit was seen for the ITT population (HR 0.88; CI: 0.78, 0.99; p=0.0365). Further analyses showed that the impact of SLD was reflected in the squamous cell carcinoma population (HR 0.92; CI: 0.77, 1.10; p=0.3649), with the greatest impact observed for squamous cell carcinoma patients with a large SLD. An impact of SLD was also seen in adenocarcinoma patients but to a lesser extent (HR 0.81; CI:0.69, 0.97; p=0.0186), as compared with the squamous cell carcinoma population. The most common AEs reported for the ITT population were diarrhea (any: 42.3 vs 21.8%; Gr ≥3: 6.6 vs 2.6%) and ALT elevations (any: 28.5 vs 8.4%; Gr ≥3: 7.8 vs 0.9%). Incidence of CTCAE Gr ≥3 AEs was 71.3 vs 64.3%. Withdrawals due to AEs (22.7 vs 21.7%) were similar in both arms, as were Gr ≥3 hypertension, bleeding or thrombosis.Conclusion
Nintedanib + docetaxel significantly reduced the risk of progression in NSCLC patients independent of histology. Adjustment for tumor burden, as represented by the SLD, led to a significant reduction in the risk of death. AEs were generally manageable with dose reductions and symptomatic treatment.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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O16.02 - Efficacy of standard care for second-line advanced non-small cell lung cancer (NSCLC) by <em>KRAS</em> mutation status: observations on MEK inhibitor enhancement of chemotherapy (ID 3329)
10:30 - 12:00 | Author(s): P.A. Jänne, D. Clemett, H. Mann, I. Smith
- Abstract
- Presentation
Background
KRAS mutations that activate the MEK/ERK pathway are found in 20–30% of NSCLC. Response to second-line therapies for advanced NSCLC may be different in the presence or absence of a KRAS mutation. MEK inhibitors are being developed in combination with cytotoxic chemotherapy for NSCLC, based on preclinical findings that MEK inhibition increases pro-apoptotic BIM levels, enhancing cytotoxic therapy, and that MEK inhibition reduces KRAS mutation-induced oncogenic drive. We reviewed available information from KRAS mutation-positive (KRAS+) and KRAS wild-type subsets in AstraZeneca clinical studies in second-line NSCLC and published data on MEK inhibitors. Our objective was to determine whether differential therapeutic activity is present in KRAS+ and KRAS wild-type populations and whether preclinical findings translate into enhanced tumour response.Methods
We reviewed data on objective clinical response in second-line NSCLC according to KRAS status in five randomised double-blind Phase II or III studies of gefitinib, vandetanib or selumetinib and three published studies of trametinib. Ninety-five percent confidence intervals (CI) around point estimates of objective response were calculated using exact (Clopper-Pearson) methods for a single proportion.Results
The studies involved 4466 patients receiving second- or later line treatment for advanced NSCLC. In total, 1286 patients received singlet chemotherapy (docetaxel or pemetrexed), including 429 with known tumour KRAS mutation status: 138 had KRAS+ and 291 had KRAS wild-type NSCLC. Additionally, 132 patients with known KRAS status received singlet chemotherapy plus a MEK inhibitor (selumetinib or trametinib): 91 with KRAS+ and 41 with KRAS wild-type NSCLC. Figure 1Conclusion
Our retrospective comparison suggests that second-line singlet chemotherapy response rates may be greater in KRAS wild-type than in KRAS+ NSCLC, and that MEK inhibition may enhance second-line chemotherapy activity in both KRAS+ and KRAS wild-type NSCLC. These observations support prospective validation of these results and further evaluation of MEK inhibitors plus chemotherapy in second-line KRAS unselected NSCLC.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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O16.03 - Cost-utility analysis of first-line treatment with erlotinib versus chemotherapy in EGFR-mutant advanced non-small-cell lung cancer (NSCLC): economic analysis of EURTAC trial (ID 1100)
10:30 - 12:00 | Author(s): A. Vergnenegre, R. Rosell, B. Massuti, P. Do, R. Corre, E. Felip, R. Palmero, R. Garcia-Gomez, F. De Marinis, M. Santarpia, E. Wright, C. Chouaid
- Abstract
- Presentation
Background
The impact of tyrosine kinase inhibitors (TKIs) in EGFR-mutant advanced NSCLC is poorly documented. Two studies (Jacob et al, ISPOR2010, Brown et al, Health Technol Assess, 2010) are based on modelisation and indirect comparisons. The present study reports a cost-utility analysis of a phase III randomized trial (EURTAC).Methods
A three state Markov model (first line PFS, second line PD and death) was built. Clinical data and resource assessment (drugs, drug administration, adverse events, second-line treatment) were collected from the trial. Utility values were derived from Nafees et al, as previously published (Vergnenegre et al. JTO 2011). Incremental cost-utility ratios (ICUR) were calculated for the first-line treatment and the overall strategy until death from the perspective of different countries (2013 actualized euros). Sensitivity analyses researched the main cost drivers.Results
The quality-adjusted life-years gained was 0.124 with erlotinib, which showed an improvement in the quality of life for these patients. Despite the extra treatment costs of second-line erlotinib in the chemotherapy arm, there was a cost benefit for erlotinib first, resulting in fewer patients receiving second-line pemetrexed along with other therapy. Cost gain in favor of first-line erlotinib was 8,918 Euros. The main results are depicted in Table1.
Sensitivity analyses will be presented at the meeting.First-line erlotinib First-line chemotherapy Average cost of first-line (euros 2013) Drugs 21,679 1030 Administration 329 4,455 Adverse events 546 2,686 Cost of post-first progression care 40,467 67,281 ICUR (erlotinib versus chemotherapy) ICUR France negative ICUR Spain negative ICUR Italy negative Conclusion
ICUR favored first-line erlotinib in EGFR-mutant patients with advanced NSCLC, which is the widely accepted treatment compared to chemotherapy. The cost-utility of the overall strategy remained beneficial in three different European countries. On behalf GFCP,GEPC and AIOT groupsOnly Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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O16.04 - DISCUSSANT (ID 3955)
10:30 - 12:00 | Author(s): J.C. Yang
- Abstract
- Presentation
Abstract not provided
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O16.05 - Efficacy, safety, and patient-reported outcomes (PROs) with crizotinib versus chemotherapy in Asian patients in a phase III study of previously treated advanced <em>ALK</em>-positive non-small cell lung cancer (NSCLC) (ID 2818)
10:30 - 12:00 | Author(s): M. Nishio, V. Hirsh, D. Kim, K.D. Wilner, A. Polli, A. Reisman, S. Iyer, F. Blackhall
- Abstract
- Presentation
Background
Crizotinib is a potent selective ATP-competitive ALK inhibitor demonstrating a high ORR in patients with advanced ALK-positive NSCLC. The main objective of the present post hoc analyses was to compare the impact of crizotinib on efficacy, safety, and PROs with that of standard second-line chemotherapy in a subgroup of patients of Asian ethnicity from the ongoing phase III study PROFILE 1007.Methods
Patients with stage IIIB/IV ALK-positive NSCLC who had received one prior platinum-based regimen were randomized to open-label crizotinib (250 mg PO BID) or chemotherapy (pemetrexed 500 mg/m[2] or docetaxel 75 mg/m[2], IV q3w). In these subgroup analyses, PFS and ORR based on independent radiologic review, OS, safety, and PROs were evaluated. PROs were assessed at baseline, on day 1 of each cycle, and at end of treatment using the validated cancer-specific questionnaire EORTC QLQ-C30 and its LC module QLQ-LC13. Time to deterioration (TTD) was defined as the time from randomization to the earliest time with a ≥10-point increase from baseline (worsening) in pain in chest, dyspnea, or cough. Repeated measures mixed-effects analyses were performed to compare change from baseline scores between the treatment arms.Results
Of 347 patients randomized, 45% were of Asian ethnicity (crizotinib, n=79; chemotherapy, n=78 [pemetrexed, 50; docetaxel, 27; no treatment, 1]). At data cutoff (March 2012), 52 Asian patients (crizotinib, 41; chemotherapy, 11) were continuing on treatment. PFS was significantly longer with crizotinib than with chemotherapy (median 8.1 vs. 2.8 months; HR, 0.53; P=0003). The ORR on crizotinib (75%) was significantly higher than on chemotherapy (22%; P<0.0001). In an interim analysis, median OS had not yet been reached in the crizotinib arm and was 22.8 months in the chemotherapy arm (HR, 0.89; P=0.347, noting that in the overall study population, only 40% of planned events had occurred and 64% of patients in the chemotherapy arm subsequently received crizotinib in another study). The most common all-causality AEs with crizotinib were diarrhea (70%), vision disorder (68%), and nausea (66%) and with chemotherapy were decreased appetite (40%), nausea (39%), and fatigue (35%). Crizotinib treatment was associated with a significantly longer TTD in LC symptoms compared with chemotherapy (median 4.2 vs. 1.6 months; HR, 0.66; 95% CI, 0.44−0.98; P=0.037). A significantly greater improvement from baseline was observed with crizotinib for global QOL (P<0.05), cough (P<0.001), dyspnea (P<0.001), pain in arm or shoulder (P<0.001), pain in chest (P<0.001), pain in other parts (P<0.05), fatigue (P<0.05), insomnia (P<0.05), and pain (P<0.001). A significantly greater improvement was observed with crizotinib compared with chemotherapy for emotional functioning (P<0.05), physical functioning (P<0.05), hair loss (P<0.001), and sore mouth (P<0.05). A significantly greater deterioration was observed in the crizotinib arm for constipation (P<0.05) and diarrhea (P<0.001) compared with chemotherapy.Conclusion
Consistent with previously reported results in the overall study population, crizotinib treatment showed significantly greater improvement in PFS, ORR, patient-reported LC symptoms, and global QOL compared with chemotherapy in a subgroup of patients of Asian ethnicity with previously treated advanced ALK-positive NSCLC, confirming the utility of crizotinib in this patient population.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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O16.06 - A phase 1 dose escalation study of a new ALK inhibitor, CH5424802/RO5424802, in ALK+ Non-Small Cell Lung Cancer (NSCLC) patients who have failed crizotinib (AF-002JG/NP28761, NCT01588028). (ID 1661)
10:30 - 12:00 | Author(s): S. Gadgeel, S. Ou, A.A. Chiappori, G. Riely, R. Lee, L. Garcia, J. Sato, S. Yokoyama, T. Tanaka, L. Gandhi
- Abstract
- Presentation
Background
Anaplastic lymphoma kinase (ALK) is a tyrosine kinase constitutively activated following chromosomal translocation in 3-7% of non-small cell lung cancer (NSCLC). These patients usually respond to the ALK inhibitor crizotinib with a median duration of response around 10 months. CH5424802 is a more potent and specific ALK inhibitor that is being studied as a treatment for NSCLC patients with ALK gene rearrangement.Methods
A phase 1 dose escalation study of CH5424802 was performed using 3+3 study design in NSCLC patients who failed crizotinib. The primary endpoint was dose limiting toxicity, and the secondary endpoints were efficacy, safety and pharmacokinetic (PK) analyses. Key eligibility criteria include prior progression on crizotinib, ECOG 0-2, adequate organ functions, confirmed ALK-rearrangement by an FDA approved test. Patients with symptomatic CNS metastases required treatment before participating. CH5424802 was administered orally at doses of 300, 460, 600, 760 and 900 mg BID until lack of clinical benefits. Intensive PK sampling was performed. Efficacy was assessed by RECIST criteria v1.1. Toxicities were evaluated by CTCAE v4.0.Results
37 NSCLC patients who have failed crizotinib and chemotherapy were enrolled in the study from 6 US sites from May 2012 to May 2013. No DLTs were observed up to the highest dose tested (900 mg BID). Only 1 patient required dose modification due to grade 2 fatigue. The most common AEs were fatigue, CPK increase, myalgia, cough, ALT increased, peripheral edema and rash. Grade 3/4 AEs include GGT increase (n=3), neutrophil decrease (n=2), hypophosphatemia, hyperglycemia, syncope, renal failure and pericardial effusion (n=1 each), but no grade 3 nausea, vomit, diarrhea, edema were reported. Preliminary efficacy was observed with PR 48% and SD 34% by investigator assessment amongst the 30 evaluable patients (See Figure of Waterfall plot). Median progression-free survival has not been reached with 27 patients (73%) remaining on study as of June 10, 2013 (median duration 85 days, range 39-347+ days). CNS activity was observed and described in the companion abstract by Ou et al. CH5424802 single dose half-life was approximately 22 hr, AUC was dose-dependent from 300 to 600 mg BID following multiple doses with a potential plateau at doses higher than 600 mg BID based on available data.Figure 1Conclusion
CH5424802 is a well-tolerated ALK inhibitor with no DLTs observed up to the highest dose tested in this study. Promising anti-tumor activity was observed in patients who have failed crizotinib.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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O16.07 - Consistent therapeutic efficacy of CH5424802/RO5424802 in brain metastases among crizotinib-refractory ALK-positive non-small cell lung cancer (NSCLC) patients in an ongoing phase I/II study (AF-002JG/NP28761, NCT01588028). (ID 1668)
10:30 - 12:00 | Author(s): S.I. Ou, S. Gadgeel, A.A. Chiappori, L. Gandhi, M. Azada, L. Garcia, I. Takaya, S. Yokoyama, T. Kamei, T. Tanaka, R. Lee, G. Riely
- Abstract
- Presentation
Background
Disease progression in brain occurs in ~50% ALK-rearranged NSCLC patients treated with crizotinib. This is likely due in part to low penetration of crizotinib into CNS. CH5424802 is a new ALK inhibitor that is effective in patients who have ALK re-arrangement. Preclinical studies in CNS implantation models suggest a promising anti-tumor activity of CH5424802 against CNS lesions. This report describes CNS activity observed in an ongoing phase I/II clinical trial.Methods
A phase I dose escalation study of CH5424802 was performed in ALK-rearranged NSCLC who have failed crizotinib. Patients received oral CH5424802 doses ranging from 300 to 900 mg BID. All patients had head CT/MRI and body CT scans at baseline, and every 6 weeks after initiation of treatment if baseline scans are positive for brain metastasis. Brain lesions without prior radiation were used to assess CNS response based on modified RECIST criteria. Simultaneous collection of cerebrospinal fluid (CSF) and plasma PK samples in selective patients is ongoing to evaluate CSF/plasma CH5424802 ratios to correlate with clinical activity in brain metastasis.Results
As of June 6, 2013, 37 patients were enrolled in the phase I study, and 31 of them were evaluable for efficacy. Preliminary overall response rate (ORR) is ~48% (15/31) in evaluable patients. 16 had brain metastases at baseline, and 2 had no prior brain irradiation but all had documented CNS progression prior to study treatment. These 16 patients received CH5424802 at 300mg (n=2), 460mg (n=2), 600mg (n=5), 760mg (n=3), and 900mg (n=4) BID. The median duration of follow-up of these 16 patients was 130+ days, with the longest being 347+ days. Activity against CNS lesions was observed as early as the first scan (3[rd] week). The preliminary CNS response is highly promising as shown in the representative scans below. Enrollment is still ongoing and CNS progression-free survival (PFS) will be presented. Currently 2 patients had simultaneous CSF and plasma levels of CH5424802, and the CSF/plasma ratios will be reported to evaluate any correlation between CSF/plasma ratios and the observed clinical activity of CH5424802 in brain metastasis.Figure 1Conclusion
CH5424802 demonstrates consistent and rapid clinical activity in brain metastases in ALK+ NSCLC patients who progressed on crizitinib. Within 3-6 weeks of treatment, CH5424802 dramatically shrinks brain lesions that progressed on crizotinib. CH5424802 could potentially replace or delay the need of brain radiation in ALK-positive NSCLC patients.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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O16.08 - DISCUSSANT (ID 3956)
10:30 - 12:00 | Author(s): D..R. Camidge
- Abstract
- Presentation
Abstract not provided
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Author of
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MO15 - Novel Genes and Pathways (ID 89)
- Event: WCLC 2013
- Type: Mini Oral Abstract Session
- Track: Biology
- Presentations: 1
- Moderators:Y. Ohe, G. Reid
- Coordinates: 10/29/2013, 16:15 - 17:45, Parkside Ballroom A, Level 1
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MO15.01 - Pathway activation mapping of KRAS wild type and mutated adenocarcinomas of the lung: new implications for patient stratification for MAP kinase pathway inhibition (ID 2705)
16:15 - 17:45 | Author(s): L. Crino
- Abstract
- Presentation
Background
KRAS proto-oncogene is one of the most frequent mutated genes in Non-Small Cell Lung Cancer (NSCLC) with greater incidence among adenocarcinomas (AD). While the clinical importance of KRAS mutation as a negative predictor for anti-EGFR therapy is not clearly understood in NSCLCs, selection of targeted therapies for KRAS mutated (MUT) patients has often focused on the inhibition of its direct downstream effectors. The aim of this study was to explore the impact of the KRAS status on the cellular signaling network of ADs of the lung harboring different KRAS mutations with a focus on ERK signaling architecture.Methods
A total of 58 AD samples were collected from chemo-naïve patients at the H. Lee Moffitt Cancer Center & Research Institute (Tampa, FL) and at S. Maria della Misericordia Hospital (Perugia, Italy). Twenty-four tumors were KRAS wild type (WT) and 34 were KRAS MUT (G12C n=18, G12V n=9, G13D n=3 and G12D n=4, respectively). All samples were subjected to laser capture microdissection and reverse phase protein microarray to quantitatively evaluate the activation status of the MAP Kinase signaling network.Results
Statistical analysis of signaling protein activation based on KRAS status revealed an overall increase in activation level of the MAPK signaling network in the KRAS MUT tumors compared to tumors expressing KRAS WT: ERK 1/2 (T202/Y204), Elk-1 (S383), p90RSK (S380), Smad2 (S245/250/255) and p70S6K (p<0.01; p<0.01; p<0.01, p=0.04 and p<0.01 respectively). Nevertheless, 6 KRAS WT patients (25%) showed activation of ERK greater than the median of the entire population and an overall MAPK signaling activation comparable to tumors harboring KRAS MUT. Eleven of the KRAS MUT tumors (32%) had ERK activation lower than the median of the population as a whole. Interestingly a high activation level of Estrogen Receptor alpha (ERα) (S118) was detected in the KRAS MUT tumors compared to the KRAS WT one (p=0.02). Moreover the nonparametric test performed to establish the correlation of activated ERK 1/2, Raf, B-Raf, C-Raf and Mek 1/2 with the expression/activation levels of the 152 endpoints analyzed in this study, revealed the activation of distinct pathways in the KRAS MUT tumors when compared to KRAS WT tumors. Significant correlations were detected with Akt, KRAS, their downstream substrates and with several receptor tyrosine kinases (p<0.0003).Conclusion
Our results suggest that MAPK signaling activation was clearly observed in KRAS MUT tumors. However, the heterogeneity in the activation level of MAPK downstream substrates within KRAS MUT and WT tumors suggests that selection of patients for MAPK targeting might benefit from the evaluation not only of the mutation itself, but also from a direct analysis of the MAPK protein network architecture. In particular the role played by ERα in KRAS MUT tumors deserves further investigations as a possible novel therapeutic target in KRAS MUT adenocarcinomas of the lung.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MO24 - NSCLC - Chemotherapy III (ID 110)
- Event: WCLC 2013
- Type: Mini Oral Abstract Session
- Track: Medical Oncology
- Presentations: 1
- Moderators:R. Feld, S. Peters
- Coordinates: 10/30/2013, 10:30 - 12:00, Parkside Ballroom A, Level 1
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MO24.02 - Treatment decisions for elderly patients with advanced non-small cell lung cancer (NSCLC) in Italian clinical practice: results from the RIGHT-3 project by Italian Association of Medical Oncology (ID 3115)
10:30 - 12:00 | Author(s): L. Crino
- Abstract
- Presentation
Background
In 2004, the Italian Association of Medical Oncology (AIOM) created the RIGHT (Research for the identification of the most effective and highly accepted clinical guidelines for cancer treatment) program. The third step of the program, RIGHT3, aimed to evaluate the concordance between AIOM lung cancer guidelines and clinical practice in Italy. Description of treatment decisions for elderly patients with advanced non-small-cell lung cancer (NSCLC) was among the indicators. According to 2009 AIOM guidelines, single-agent chemotherapy with a third-generation agent was a reasonable choice for elderly patients with advanced NSCLC, whilst evidence about use of platinum-based treatment in the elderly population was judged potentially affected by selection bias and not conclusive.Methods
RIGHT3 was a retrospective observational study conducted in a sample of 53 Italian lung cancer centers, representative of 230 AIOM centers. Patients with NSCLC diagnosis who had their first visit at the oncology center during 2010 and followed-up for at least 6 months were included. Proportion of elderly patients with stage IV disease receiving chemotherapy was among the 14 indicators evaluated.Results
Overall, 306 pts with stage IV NSLSC were enrolled, and 299 were evaluable. Of these, 91 (30.4%) were older than 70. In the elderly subgroup, 81 pts (89%) were treated with first-line chemotherapy. In detail, a single-agent treatment was administered in 28 (34.6%) of cases, and a combination chemotherapy in the other 53 cases (65.4%). Among pts receiving platinum-containing doublets, carboplatin was more frequently used than cisplatin: carbo-gemcitabine (16 pts), carbo-pemetrexed (12 pts), cisplatin-pemetrexed (8 pts), cisplatin-gemcitabine (7 pts), carbo-vinorelbine (4 pts) were the 5 most frequently used regimens.Thirty pts (33%) received a second-line chemotherapy: single-agent in 23 cases, combination chemotherapy in 7 cases.Conclusion
First-line platinum-based combination chemotherapy was commonly used in elderly patients with advanced NSCLC in 2010 by the Italian Lung cancer centers involved. First-line single-agent treatment, recommended by AIOM 2009 guidelines as the treatment choice with highest level of evidence, was used only in a minority of patients.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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O03 - NSCLC - Targeted Therapies I (ID 113)
- Event: WCLC 2013
- Type: Oral Abstract Session
- Track: Medical Oncology
- Presentations: 1
- Moderators:J. Ross, J.C. Yang
- Coordinates: 10/28/2013, 10:30 - 12:00, Bayside Auditorium B, Level 1
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O03.02 - Randomized Phase-3 trial (INSPIRE) of Necitumumab plus Cisplatin-Pemetrexed versus Cisplatin-Pemetrexed Alone as First-Line Therapy in Stage IV Non-Squamous NSCLC (ID 2337)
10:30 - 12:00 | Author(s): L. Crino
- Abstract
- Presentation
Background
Necitumumab is a human IgG1 anti-EGFR1 monoclonal antibody that competes for the binding of natural ligands to this receptor and prevents receptor activation. EGFR1 is detectable in approximately 85% of advanced NSCLC tumors. This phase 3 study investigated necitumumab in combination with first-line chemotherapy in advanced non-squamous NSCLC.Methods
Patients with histologically or cytologically proven stage IV non-squamous NSCLC were randomized 1:1 to either Arm A: cisplatin 75mg/m[2] i.v.-pemetrexed 500mg/m[2] i.v. (Cis + PEM) on Day 1+ necitumumab 800mg i.v. on Days 1 and 8 of a 21-day cycle or Arm B: Cis+PEM alone. Patients received these regimens for up to six cycles. For patients in Arm A with at least stable disease, necitumumab continued until PD or intolerable toxicity. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), safety, and EGFR protein expression level by immunohistochemistry (H-score) utilizing archived tumor tissue based on a mandatory tissue collection. The planned sample size of this study was 947 patients (assuming a hazard ratio [HR] of 0.8 would allow 85% power at 2-sided alpha level of 0.05). After 633 patients, enrollment was stopped (after Feb 2011) following an Independent Data Monitoring Committee (IDMC) recommendation.Results
Between Nov 2009 and Feb 2011 633 patients were randomized (315 Arm A; 318 Arm B). Baseline characteristics were balanced between the arms; 67.0% were male and 33.0% female; ECOG-PS 0/1 94.2 % and PS 2 5.7 %. No difference between treatment arms was observed for OS (median 11.3 vs 11.5 months; HR 1.01 95%-CI [0.84, 1.21]), PFS (median 5.6 vs 5.6 months, HR 0.96 95%-CI [0.80, 1.16]) and ORR (31.1 vs 32.1%; Odds ratio 0.96 95%-CI [0.68, 1.34]). The exploratory analysis in 490 patients assessable for H-score revealed no association between H-score and differences in efficacy between treatment arms (H-score < 200: mOS 8.97 vs 9.72 months, HR 1.07, mPFS 4.90 vs 4.76 months, HR 0.95, ORR 27.1 vs 26.0%; H-score ≥ 200: mOS 15.01 vs 13.34 months, HR 1.03, mPFS 5.59 vs 5.62 months, HR 0.94, ORR 39.6 vs 39.4%). Grade ≥ 3 treatment-emergent adverse events (AEs) occurring more frequently in Arm A included skin or subcutaneous disorders (14.1 vs 0.3%), thromboembolic events (9.5 vs 6.4%), hypomagnesaemia (7.6 vs 2.2%), asthenia (6.9 vs 1.9%), vomiting (6.6 vs 3.2%), dyspnea (5.3 vs 2.6%) and diarrhea (4.3 vs 2.2%). The frequency of study drug related deaths was 4.9% and 2.9% in Arms A and B, respectively.Conclusion
In this study, the addition of necitumumab did not improve the efficacy outcome over cisplatin plus pemetrexed alone in advanced non-squamous-NSCLC. The EGFR H-score did not seem to predict the efficacy outcomes of necitumumab in combination with cisplatin plus pemetrexed. The addition of necitumumab resulted in a higher frequency of grade ≥ 3 AE (skin reaction, GI, asthenia and other) and an imbalance of grade ≥ 3 thromboembolic events. Further biomarker studies are ongoing.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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P1.02 - Poster Session 1 - Novel Cancer Genes and Pathways (ID 144)
- Event: WCLC 2013
- Type: Poster Session
- Track: Biology
- Presentations: 2
- Moderators:
- Coordinates: 10/28/2013, 09:30 - 16:30, Exhibit Hall, Ground Level
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P1.02-005 - Prognostic role of expression levels of FABP3, H19, TFPI2, AKR1B10 CYP3A5, SCGB3A2 genes in adenocarcinoma stage I patients (ID 3208)
09:30 - 16:30 | Author(s): L. Crino
- Abstract
Background
In resected lung cancer, no reliable clinical or molecular predictors are currently available for identifying patients with high risk for developing recurrent disease. In a previous study, we compared gene expression profiling from adenocarcinoma specimens and normal lung tissue with non relapse (NR) and early relapse (ER), using Affimetrix human microarray HG-U133Plus 2.0. We selected 5 genes up-regulated and 4 genes down-regulated were predictive for clustering patients in ER and NR (Siggillino et al. ECCO 2011). Here, we validate our results using an independent cohort of patients with lung adenocarcinoma stage I to identify novel genes involved in the risk of ER compared to NR disease.Methods
From tissue banking of 180 consecutive resected NSCLC stage I patients at two Italian institutions, we selected 58 frozen specimens of lung adenocarcinoma tissue with corresponding normal lung. Total RNA was isolated from tumor and normal lung specimens using RNA Universal Tissue Kit and automatically purified by Biorobot-EZ1 instrument (Qiagen). Quantification of mRNA expression levels of 9 genes (5 up-regulated: CLCA2, FABP3, H19, TFPI2, AKR1B10 and 4 down-regulated: CYP3A5, ALDH3A1, SCGB3A2, SCGB1A1, were analyzed by real-time one-step RT-PCR using QuantiFast technology by RotorGeneQ instrument (Qiagen), and the results were compared considering β-actin as the internal reference gene and as calibrator the pool of normal tissues of analyzed patients. The gene expression of all evaluated genes and their association with relapse disease measures were assessed by t-test and logistic regression model was used for multivariate analysis.Results
Fifteen-eight adenocarcinoma stage I patients were evaluable, 17% of which had an ER. Patients characteristics were as follows: median age was 65.8 years (38.7-81.5), 67.2% were male, 91.3% were PS 0, 70.7% were ever-smokers. The expression median values of 9 genes: CLCA2, FABP3, H19, TFPI2, AKR1B10, CYP3A5, ALDH3A1, SCGB3A2, SCGB1A1 were 0.30, 0.71, 0.34, 1.10, 0.26, 0.24, 0.42, 0.53, 0.09, respectively. Among all genes evaluated, the NR vs ER mean expression levels of two genes down-regulated (CYP3A5, 1.09 vs 0.30; SCGB3A2, 2.28 vs 0.98) and two genes up-regulated (AKR1B10, 4.53 vs 34.20; FABP3 1.25 vs 1.55) were superimposable respect to the results of previous microarray analysis. The median disease free survival (DFS) and overall survival (OS) were 21 and 23 months, respectively. In the logistic multivariate analysis the mean expression levels of all genes showed a tendency to predict the ER in the overall population (p=0.07). Nevertheless considering only the expression levels of genes (FABP3, H19, TFPI2, AKR1B10, CYP3A5, SCGB3A2) identified as significant with t-test, the covariates in multivariate analysis increased their capacity of ER prediction (p= 0.028).Conclusion
Our results indicate that it is possible to define, through gene expression, a characteristic gene profiling of early relapse tumor patients with an increased risk of relapse disease. The contemporary expression levels of 6 genes (FABP3, H19, TFPI2, AKR1B10, CYP3A5, SCGB3A2) predicted a worse DFS. Such features may have important implications for future targeted therapies. We thank Italian Association for Cancer Research (AIRC) for supporting the study. -
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P1.02-006 - Identification of targetable driver mutations in molecularly selected never smoker lung adenocarcinomas (ID 2970)
09:30 - 16:30 | Author(s): L. Crino
- Abstract
Background
Approximately 25% of lung cancers occur in lifelong never smokers. Although no dominant risk factor has been identified yet, the discover of molecular drivers potentially targetable with biological agents, makes lung cancer in never smokers a unique disease, candidate for a personalized therapy. Through the FISH test, we performed a screening for ALK, ROS1, and RET rearrangements, in a highly selected population of lung adenocarcinoma never smoker patients, previously demonstrated to be wild-type for EGFR and K-RAS mutations.Methods
We collected archived histological material of 28 EGFR and K-RAS wild-type patients (pts), from a 200 never-smoker advanced lung adenocarcinomas database, to be analyzed for the presence of rearrangements in ALK, ROS1 and RET genes. All pts were treated at the Division of Medical Oncology of the S Maria della Misericordia Hospital in Perugia from October 2003 to February 2013. 20 specimens were included in a tissue microarray (TMA) analysis, whereas 8 were screened in separate subset, due to the scarce samples. FISH test was performed using a combination of commercial reagents and custom designed probes. Median overall survival (OS) of mutated pts compared to the pan-negative ones, was evaluated by Cox multivariate analysis.Results
Clinicopathological characteristics: among the 28 patients, 27 were never smokers and 1 former light smoker, with a good performance status; 20 (72%) presented with a metastatic disease at diagnosis, 8 (28%) were locally advanced; median age was 56 years-old, with a predominance of female sex (18/28, 64%). All cases were invasive adenocarcinomas and classified into 18 (64%) solid predominant type, 1 (3.5%) mixed acinar/lepidic pattern, 1 (3.5%) papillary, no predominant subtype for 8 (28%) patients, because of unsufficient histological material available. Of the 28 never smoker cases, we identified 7 gene fusions (25%), including 2 pts ALK+ (7.1%), 3 pts ROS1+ (10.7%) and 2 RET+ cases (7.1%), one compatible with KIF5B:RET and other with CCDC6:RET fusion. Median OS for the entire cohort was 24.5 months (mo), 61.2 mo for mutated pts (any rearrangement) vs 24.1 mo for not-mutated, respectively (P = .292).Conclusion
Molecularly selected never smoker lung adenorcinomas associates with a high incidence of driver genes mutations and further investigations to confirm our frequencies in larger cohorts are needed. In line with literature data, our findings suggest a different survival outcome among genotypes, and identification of specific subsets in this special population can lead to successful treatment with target therapies.
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P1.06 - Poster Session 1 - Prognostic and Predictive Biomarkers (ID 161)
- Event: WCLC 2013
- Type: Poster Session
- Track: Biology
- Presentations: 1
- Moderators:
- Coordinates: 10/28/2013, 09:30 - 16:30, Exhibit Hall, Ground Level
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P1.06-041 - Prognostic impact of cytoskeleton regulatory protein human Mena (hMena) isoforms in resected, node-negative, non-small-cell lung cancer: validation of a clinic-molecular prognostic model. (ID 2609)
09:30 - 16:30 | Author(s): L. Crino
- Abstract
Background
Human Mena and the isoform hMena[+11a] are cytoskeleton regulatory proteins involved in adhesion, motility, regulated in the epithelio-mesenchimal transition. Here, we investigated their potential prognostic value in node-negative non-small-cell lung cancer (NSCLC) patients.Methods
Pan-hMena, hMena[+11a], E-cadherin, vimentin, ER-beta, EGFR, HER-2, pAKT, detected immunohystochemically on duplicate TMA and clinical factors (sex, age, histology, grading, T-size, number of resected nodes, RN) were correlated to 3-yr disease-free (DFS), cancer-specific (CSS), and overall survival (OS) using a Cox model. ROC analysis provided optimal cut-off values and model validation. A logistic equation including regression analysis coefficients was constructed to estimate individual patients’ probability (IPP) of relapse. Internal cross-validation (100 simulations with 80% of the dataset) and external validation was accomplished.Results
In a training set of 248 patients (median follow-up: 36 months, range 1-96), Pan-hMmena and hMena+11a were the only biological variables displaying significant correlation with outcome(s), confirmed by the cross-validation (replication rate: 78%, 83%), with a prognostic model accuracy of 61% (standard error 0.04, p=0.0001). Patients with high pan-hMENA expression had a non-significant trend towards a worse outcome, while patients with high hMena+11a expression had a significant and borderline significant advantage in DFS (p=0.03) and OS (p=0.056), respectively, and a non-significant trend towards a better CSS. Univariate and multivariate 3-yr median individual patient probabilities of recurrence were 70.9 (range 40.3-94.4) and 41.2 (range 13.6-86.5), respectively (data not shown). The subgroup of patients with High Pan-hMena/Low hMena11a relative expression fared significantly better than any of the other 3 groups (p≤0.002 for all outcomes). On the basis of the combination between this molecular hybrid variable and T-size and RN, a 3-class risk stratification model was generated; the derived 3-risk class survival model strikingly discriminated between patients at different risk of relapse, cancer-related death, and death for any cause, with a prognostic accuracy of 61% (standard error 0.03, p=0.01), according to ROC analysis. The 3-risk class survival model was externally validated in an independent dataset of 133 patients, and significantly discriminated between patients at Intermediate- and High-Risk of relapse and cancer-related death.Conclusion
The expression of the hMena and its isoform may represent a powerful prognostic factor in early NSCLC and usefully complements clinical parameters to accurately predict individual patient risk..
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P1.11 - Poster Session 1 - NSCLC Novel Therapies (ID 208)
- Event: WCLC 2013
- Type: Poster Session
- Track: Medical Oncology
- Presentations: 1
- Moderators:
- Coordinates: 10/28/2013, 09:30 - 16:30, Exhibit Hall, Ground Level
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P1.11-033 - Afatinib in EGFR mutant non-small-cell lung cancer patients with acquired resistance to reversible EGFR-TKIs (ID 2285)
09:30 - 16:30 | Author(s): L. Crino
- Abstract
Background
Afatinib, an irreversible EGFR-HER2 dual inhibitor, demonstrated superiority versus standard platinum-based chemotherapy as front-line therapy in non-small-cell lung cancer patients (NSCLC) with activating Epidermal Growth Factor Receptor (EGFR) mutations. In pretreated NSCLC afatinib failed to improve survival when compared to placebo in patients refractory to gefitinib or erlotinib and not selected for EGFR status. Aim of the present study was to evaluate clinical efficacy of afatinib in EGFR mutant NSCLC patients (pts) with secondary resistance to reversible EGFR-TKIs.Methods
We retrospectively analyzed a cohort of 97 EGFR mutant lung cancer pts resistant to EGFR-TKI according to criteria used in the LUX-Lung 1 trial (Miller VA, Lancet Oncol 2012) and treated with Afatinib at the daily dose of 40-50 mg. The drug was given as compassionate use.Results
The study included individuals with a median age of 62,5 year. The majority were females (N=63/64.9%), never/former smokers (N=94/96,9%), with good performance status (ECOG PS 0-1; N=90/90.2%) and pretreated with > 3 therapy lines (N=68/70.0%). EGFR status was assessed in tumor tissue obtained at the time of original diagnosis. The majority of pts (N=64, 66%) harbored a deletion in exon 19, while T790M mutation was detected in two cases including one case with double exon 19 and T790M mutation. Among the 95 pts evaluable for toxicity, 54.7% had any grade skin rash, including 11.6% with grade 3, and 50,5% had any grade of diarrhea, with grade 3 recorded in 10,5%. Among the 87 pts evaluable for efficacy, response rate (RR) was 11.5%, with a median progression free-survival and overall survival of 3.9 months and 7.3 months respectively. In 25 pts a tumor biopsy was repeated immediately before starting Afatinib therapy and 1 patient out of 5 individuals harboring T790M mutation showed a short extracerebral partial response, with following brain progression.Conclusion
Our findings suggest that afatinib is modestly effective in EGFR mutant NSCLC with acquired resistance to reversible EGFR-TKIs.
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P2.06 - Poster Session 2 - Prognostic and Predictive Biomarkers (ID 165)
- Event: WCLC 2013
- Type: Poster Session
- Track: Biology
- Presentations: 1
- Moderators:
- Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level
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P2.06-028 - ERCC1 mRNA expression and KRAS mutation status in EGFR wild type (WT) advanced non-small cell lung cancer (NSCLC) patients (ID 2405)
09:30 - 16:30 | Author(s): L. Crino
- Abstract
Background
In a previous report of EGFR WT advanced NSCLC patients treated with first-line platinum-based chemotherapy we observed a worse clinical outcome for KRAS-mutants compared with KRAS WT patients (Metro et al. ESMO 2012). Here, we assessed whether this phenomenon could be due to different levels of ERCC1 expression.Methods
From a prospectively maintained database of EGFR WT advanced NSCLC patients diagnosed at a single Institution between January 2006 and November 2012, we identified the individuals who had a known KRAS mutation status and tissue available for assessment of ERCC1 mRNA expression. Total RNA was isolated from paraffin-embedded tumor specimens using RNeasy Mini kit and automatically purified by QiaCube instrument (Qiagen). Quantification of mRNA expression levels of ERCC1 was analyzed by real-time one-step RT-PCR using QuantiFast technology by RotorGeneQ instrument (Qiagen), and the results were compared considering β-actin as the internal reference gene.Results
One hundred and eleven patients were evaluable, 60 of which were KRAS-mutants. Among KRAS-mutants, the rate of codon 12/13/61 mutations were 80%/13.3%/6.7% respectively. Baseline patients characteristics were as follows: median age was 62 years (35-84), 36.9% were male, 63.9% were stage IV, 78.3% were PS 0 or 1, 87.3% were ever-smokers, and 71.1% had received a first-line platinum-based chemotherapy. More ever-smokers were present in the KRAS-mutant subgroup compared with WTs (90% versus 76.5%, respectively, P = 0.08). ERCC1 average scores ranged from 0.1 to 26.7, the values being not normally distributed (Kolmogorov-Smirnov test, P<0.0001). Median and mean overall ERCC1 values for all patients were 1.3 and 2.2 [standard deviation (SD) 3.4], respectively. There was no statistically significant difference in terms of ERCC1 median values betwen KRAS-mutants and KRAS WTs (1.4 vs. 1.3, respectively, P = 0.27). Nevertheless, mean ERCC1 expression levels were found to be significantly higher in KRAS-mutants compared with KRAS WTs [2.9 (SD 4.5) vs. 1.4 (SD 0.8), respectively, P = 0.02]. This finding was due to 7 KRAS-mutant patients (ERCC1 high) coming out with ERCC1 levels higher than 5.0, thus notably incresing mean ERCC1 values. In the group of patients treated with first-line platinum-based chemotherapy (n = 79), median progression-free survival was 1.9 months for KRAS-mutant, ERCC1 high patients (n = 6), 5.1 months for KRAS-mutant, ERCC1 low patients (n = 38), and 7.1 months for KRAS WT patients (n = 35) (P = 0.003).Conclusion
KRAS-mutant NSCLCs may express higher levels of ERCC1 compared with KRAS WTs, which could translate into poor sensitivity to first-line platinum-based chemotherapy. Combination strategies of platinum-based chemotherapy plus KRAS-targeting agents may represent an appealing upfront strategy for KRAS-mutants advanced NSCLCs, particularly in presence of concomitant expression of high ERCC1 levels.
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P2.24 - Poster Session 2 - Supportive Care (ID 157)
- Event: WCLC 2013
- Type: Poster Session
- Track: Supportive Care
- Presentations: 1
- Moderators:
- Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level
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P2.24-048 - Prevalence of pulmonary embolism in patients with oncogene addicted advanced lung adenocarcinoma (ID 2967)
09:30 - 16:30 | Author(s): L. Crino
- Abstract
Background
Non-small cell lung cancer is associated with a higher risk of thromboembolic events in comparison with SCLC. Adenocarcinoma represent roughly 75% of NSCLC patients. Lung adenocarcinomas harboring EGFR and KRAS mutations as well as EML4/ALK rearrangements represent distinct subsets of this disease. No data are available concerning the prevalence of pulmonary embolism in lung adenocarcinoma patients with these mutations. The aim of the study was to evaluate the prevalence of pulmonary embolism in patients with stage IIIB and IV lung adenocarcinomas harboring EGFR and KRAS mutations as well as EML4/ALK traslocations.Methods
Patients with stage IIIB or IV NSCLC referred to Division of Medical Oncology at the Hospital of Perugia between 2008 and 2012 were included in the study. In these patients, contrast-enhanced CT scans of the chest were reviewed for the presence of pulmonary embolism by a panel composed by three radiologists. In the same patients, data regarding the molecular characteristics (EGFR exons 18-21 and KRAS exon 2 mutations as well as EML4/ALK traslocations) were collected.Results
A total of 209 patients with stage IIIB or IV NSCLC were included in the study. A histologic diagnosis of lung adenocarcinoma was done in 173 patients (82.7%). In 127 of these patients sequence analysis for known EGFR (exon 18-21) and KRAS (exon 2) mutations was performed. In this population 31/173 patients were EGFR mutated (17.9%), 27/173 were K-RAS mutated (15.6 %) and 17/173 were EML4/ALK positive (9.8%). 41 patients with lung adenocarcinoma had a diagnosis of pulmonary embolism at CT scan (23.7%). Of these, 34.1% had no oncogene mutations in comparison with 28.8% of the patients without pulmonary embolism. Of the 41 patients with a diagnosis of pulmonary embolism 12.1% had an EGFR mutation and 12.1% a KRAS mutation, in comparison with 19.7% and 16.6% of patient without pulmonary embolism, respectively. In patients with lung adenocarcinoma, EML4/ALK rearrangements was observed in 19.5% among patients with pulmonary embolism and in 6.8% among patients without it. The risk of pulmonary embolism was 3.3-fold higher in presence of EML4/ALK rearrangements in comparison with no EML4/ALK rearrangements [OR: 3.3 (95%CI 1.2-9.2)].Conclusion
In lung adenocarcinoma patients, the presence of EML4/ALK traslocation seems to be associated with a high risk of pulmonary embolism and could help in identifying patients at particular high risk who might benefit from an antithrombotic prophylaxis. These preliminary data need to be confirmed by further studies.
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P3.24 - Poster Session 3 - Supportive Care (ID 160)
- Event: WCLC 2013
- Type: Poster Session
- Track: Supportive Care
- Presentations: 1
- Moderators:
- Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level
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P3.24-048 - Prevalence of unexpected pulmonary embolism at contrast-enhanced CT scan performed for cancer staging in patients with advanced lung cancer (ID 3111)
09:30 - 16:30 | Author(s): L. Crino
- Abstract
Background
Patients with advanced lung cancer have been reported to be at high risk for venous thromboembolism (VTE). In patients with cancer, a rate of unexpected pulmonary embolism (UPE) of about 1.5% has been reported.The aim of the study was to determine the prevalence of UPE in patients with stage IIIB or IV NSCLC or extensive SCLC who underwent CT scans for cancer staging.Methods
We reviewed the contrast-enhanced CT scans of the chest performed for routine cancer staging in consecutive patients with advanced lung cancer (stage IIIB or IV NSCLC or extensive SCLC) referred to the Division of Medical Oncology at the hospital of Perugia between 2008 and 2012. All CT scans were reviewed by an ad hoc panel composed by 3 radiologists. PE was defined as unexpected when a filling defect in central, lobar, segmental or sub-segmental pulmonary arteries was observed in absence of clinical suspicion of PE.Results
Overall, 223 patients were included in the analysis: 180 patients with stage IV-NSCLC, 24 patients with stage IIIB-NSCLC, and 19 patients with extensive SCLC. A total of 899 CT scans were reviewed. The prevalence of UPE was 19.7% (44/223): 34 (77.3%) in patients with stage IV-NSCLC, 7 (15.9%) in patients with stage IIIB-NSCLC, and 3 (6.8%) in patients with advanced SCLC. Patients with UPE were 26 males and 18 females and had a mean age of 58 years (range 24-78). UPE was monolateral in 30 patients and bilateral in 14 patients. UPE involved central pulmonary arteries in 6 patients, lobar arteries in 16 patients and segmental arteries in 19 patients. 3 patients had an isolated sub-segmental UPE. The mean time between cancer diagnosis and UPE was 11.8 months. 27% of cancer patients with UPE had the positive CT scan at diagnosis and 50% within 3 months. A recurrence of UPE was observed in one patient.Conclusion
Patients with stage IIIB or IV NSCLC or extensive SCLC have a high rate of UPE at CT scan performed for cancer staging. UPE was bilateral in about one third of patients. A minority of UPE involved isolated sub-segmental arteries.
