ASCO2013摘要

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错了  中文版的摘要。

10563 General Poster Session (Board #46E), Sat, 1:15 PM-5:00 PM
A large retrospective analysis of trabectedin in 885 patients with advanced soft tissue
sarcoma.
Axel Le Cesne, Isabelle Ray-Coquard, Florence Duffaud, Christine Chevreau, Nicolas Penel, Binh Bui,
Sophie Piperno-Neumann, Corinne Delcambre, Maria Rios, Loic Chaigneau, Christine Le Maignan,
Cecile Guillemet, François Bertucci, Emmanuelle Bompas, Claude Linassier, Olivier Collard,
Caroline Even, Francoise Ducimetiere, Philippe Cousin, Jean-Yves Blay; Institut Gustave Roussy, Villejuif,
France; Centre Léon Bérard, Lyon, France; Hopital de la Timone, Marseille, France; Institut Claudius
Regaud, Toulouse, France; Centre Oscar Lambret, Lille, France; Institut Bergonie, Bordeaux, France;
Institut Curie, Paris, France; Centre François Baclesse, Caen, France; Centre Alexis Vautrin, Vandoeuvre- lès-Nancy, France; Institut Regional du Cancer en Franche-Comté - University Hospital, Besançon, France; Centre Hospitalier Universitaire Saint Louis, Paris, France; Centre Henri Becquerel, Rouen, France; Institut Paoli Calmettes, Marseille, France; Centre René Gauducheau, Nantes St Herblain, France; Department of Medical Oncology, Centre Hospitalier Universitaire Tours, Tours, France; Institut de Cancérologie de la Loire, St. Priest en Jarez, France
Background: Trabectedin (Yondelis) is the first marine-derived antineoplastic drug approved in Europe for the treatment of patients with recurrent ASTS or for patients unsuited to receive anthracyclines and ifosfamide. We retrospectively analyzed the RetrospectYon database with patients’ data treated with trabectedin between Jan 2008 - Dec 2011. Methods: Trabectedin was given at the approved dose of 1.5 mg/m2 as a 24-h infusion every 3 weeks. Patients who achieved partial response (PR) or stable disease (SD) after 6 cycles could receive maintaining trabectedin treatment. Uni- and  ultivariate analyses of prognostic factors were performed. Results: 885 patients (486 women) from 26 centers in France with ASTS with a median age of 54 years (range 12-84) were included. Most had leiomyosarcoma (36%), liposarcoma (18%) or synovial STS (11%). At baseline, performance status (PS) was 0 in 26%, 1 in 47% and .1 in 27% of  patients. A median of 4 trabectedin cycles (range 1-28) was given as a 2nd (41%), 3rd (39%) or $4th (20% of patients) treatment line. Toxic death and unscheduled re-hospitalization occurred in 0.5% and 8% of patients, respectively.The objective response rate was 15% (6 complete and 127 PR), and SD rate was 45.5% (n5403). After a median follow-up of 22.6 months (range 0.03-51.2), the patients who received trabectedin as 2nd
, 3rd or $4th line had the median PFS of 4.3, 4.2 and 3.4 months, respectively, and the median OS of 12.9, 12.3 and 9.5 months. Multivariate analysis identified liposarcoma, leiomyosarcoma, angiosarcoma,undifferentiated pleomorphic sarcoma (UPS) and trabectedin line as independent prognostic factors for PFS, and UPS, angiosarcoma, rhabdomyosarcoma, gender, PS and trabectedin line for OS. After 6 cycles, 205 of the 273 patients with non-progressive disease received trabectedin as maintenance treatment and obtained a superior PFS (median 11 vs. 7.2 months, p50.0001) and OS (median 25.1 vs. 16.9 months, p,0.0001) that those who stopped trabectedin after 6 cycles. Conclusions: Patients with ASTS treated with trabectedin ha PFS and OS comparable or better to those observed in phase II/III trials. Trabectedin maintenance beyond 6 cycles is associated with improved OS and warrants further exploration.

10572 General Poster Session (Board #47F), Sat, 1:15 PM-5:00 PM
Metronomic continuous oral cyclophosphamide as second and further line in
soft-tissue sarcomas (STS) of the adult.
Alessandro Comandone, Antonella Boglione, Elena Giubellino, Paola Bergnolo, Giancarlo Gino,
Elena Maria Brach del Prever, Marco Turbiglio, Raimondo Piana, Paolo Pochettino, Alessandra Linari,
Orietta Dal Canton, Simona Chiado Cutin, Ferdinando Garetto, Cristiano Oliva, Davide Ottaviani,
Paola Pazienza; Piedmontese Group for Sarcomas/Italian Sarcoma Group, Torino, Italy; Piedmontese
Group for Sarcomas/Italian Sarcoma Group, Turin, Italy
Background: In STS third line treatment is poorly defined. However many patients (pts), after aggressive therapy as first and second line progress in their disease ask to be treated. Oral cyclophosphamide (CPM) was already used in breast cancer, prostate cancer and in elderly pts with STS with favourable results. Aim of our study was to define the feasibility, tolerability and activity of oral CPM as third line and further line chemotherapy Methods: 45 pts (19 M; 26 F) with advanced or metastatic STS heavily pretreated were included. Oral CPM was given daily at total dose of 50 mg/day without interruption excepted for toxicity or progressive disease Results: Median age was 60 (32-81), histological subtypes were: leiomyosarcoma 12, liposarcoma 10, condrosarcoma 5, sinovialsarcoma 4, sarcoma NOS 4, other 10. Primary sites were: extremities 21, retroperitoneum 19, trunk 5. 41 pts were metastatic, 4 locally advanced. 41 pts werepretreated with chemotheraphy (15  were in II line, 17 in III line, 7 in IV line, 2 in V line). Median PS (ECOG) was 2 . Median duration of theraphy was 4 months (1-38). Progression free survival (PFS) ranged from 0 to 421 months (median 4 months). Treatment was well tolerated, we registred only one episode of leucopenia G2 and one of asthenia G2. No complete responses were seen. Only 3 minimal responses and 18 stable disease were seen. Conclusions: Oral CPM showed a mild activity and good tolerability in advanced soft tissue and metastatic STS. It could be an appropriate solution as second line and further
therapy and in unfit or elderly pts。

10576 General Poster Session (Board #48B), Sat, 1:15 PM-5:00 PM
Safety of trabectedin (T) in elderly patients (pts) with advanced soft tissue sarcoma
(STS).
Roberta Sanfilippo, Giacomo Giulio Baldi, Elena Fumagalli, Andrea Marrari, Rossella Bertulli,
Elena Palassini, Silvia Stacchiotti, Michela Libertini, Paolo Giovanni Casali; Fondazione IRCCS Istituto
Nazionale dei Tumori, Milan, Italy; Medical Oncology Unit, Prato, Italy
Background: T is a marine-derived cytoxic alkaloid approved in the European Union for further-line
chemotherapy of advanced STS. Most common side effects are fatigue, neutropenia and transient
transaminitis. Overall the drug is well tolerated with no cumulative toxicity. Studies in elderly pts are
lacking. Methods: We retrospectively reviewed all pts $65 year-old, with pre-treated advanced STS, who received T at our Institution from January 2002 to January 2013, focusing on tolerability. All patients received premedication with dexamethasone 4 mg p.o. bid 24 hours prior to T  ministration. Treatment toxicity was graded according to CTCAE (v 4.0). Results: Fourty-two pts were identified (males 5 22, females 5 20; median age 5 69 years, range 65-82; ECOG PS 0 5 1 pt, 15 38 pts and 2-35 3 pts; main histotypes 5 22 liposarcoma: 12 myxoid-round cell liposarcoma, 10 well/dedifferentiated liposarcoma, 17 leiomyosarcoma, 2 synovial sarcoma, 4 others; disease extent 5 34 metastatic and 8 locally advanced; median line of administration of T5 3rd , range 1st
-5th ; median T dose 5 2.2 mg, range 5 2.7-1.7 mg). A total of 319 cycles were administered (median 6, range 5 1-23). Starting dose was 1.3 mg/mq in 37 pts and 1.1 mg in 5 pts. The most common side effects were: fatigue (all grades: 19% of cycles), reversible myelosuppression, mainly neutropenia (grade 3-4: 50%), transient transaminitis (grade 3-4: 21%). Eighteen pts needed a dose reduction: inter-cycle transient transaminitis (3 pts), neutropenia ( 13 pts), asthenia (2 pts).
In 7 patients, cycles needed to be delayed as well. Three pts interrupted T due to toxicity: grade 3
thrombocytopenia in 1 pt and grade 4 neutropenia in 2 pts. Conclusions: This retrospective analysis
confirms that T is well tolerated in elderly pts. No major differences were found in the safety profile
compared to historical controls, except a higher incidence of myelosuppression, which however was not influential on subsequent T administration.

Proteomic Stratification Test Can Help Guide Second-Line Treatment of NSCLC
A simple serum protein test can help guide treatment decisions between chemotherapy and erlotinib as second-line therapy for patients with non–small-cell lung cancer (NSCLC), according to results of a phase III study presented at the annual meeting of the American Society of Clinical Oncology in Chicago.

“EGFR tyrosine kinase inhibitors are more effective in NSCLC patients with EGFR activating mutations, but we know the majority of non-Asian patients with NSCLC are EGFR-wildtype or are never tested for EGFR status,” said Vanesa Gregorc, MD, of San Raffaele Scientific Institute in Milan, Italy, who presented results of the PROSE study. “For patients without EGFR activating mutations or unknown EGFR status being considering for treatment with EGFR-TKIs, there is a need for other predictive markers.”




The VeriStrat test (Biodesix) is a serum protein expression test. In the PROSE study, patients were tested prior to randomization and categorized as either VeriStrat-Good (VS-G) or VeriStrat-Poor (VS-P); they then received either erlotinib or chemotherapy with pemetrexed(Drug information on pemetrexed) or docetaxel(Drug information on docetaxel). There were 129 chemotherapy patients, with 88 (68%) classified VS-G and 41 (32%) classified VS-P; the erlotinib group had 134 patients, and 96 (72%) were VS-G and 38 (28%) were VS-P.

The median overall survival was 9 months in the entire chemotherapy group and 7.7 months in the erlotinib group, for a hazard ratio of 1.14 (95% CI, 0.88–1.49; P = 0.313). The overall survival was similar between the VS-G patients: 10.92 months in VS-G chemotherapy patients and 10.95 months in VS-G erlotinib patients.

There was a significant difference, however, between VS-P patients on either therapy. VS-P patients in the chemotherapy group survived a median of 6.38 months, compared to only 2.98 months in the VS-P group receiving erlotinib. Overall, the VeriStrat treatment interaction was significant; the test’s classification, along with ECOG performance status, were found to be significant predictors of treatment outcome.

Dr. Gregorc concluded that patients stratified as VS-P, which will make up about 30% to 35% of patients, have better survival with chemotherapy than with erlotinib. “Serum proteomic VeriStrat classification is clinically useful to guide treatment decisions in NSCLC patients with unknown or wildtype EGFR status in second-line setting,” she said.

Luis Paz-Ares, MD, PhD, of the Hospital Universitario Virgen del Rocio in Sevilla, Spain, was the Discussant for the session, and said this study suggests “we may have another useful biomarker.” The results, he said, confirm that VeriStrat is both prognostic and predictive of treatment outcome, and noted that other trials including one called EMPHASIS-lung, are ongoing to confirm the test’s utility.

ASCO: NSCLC Tumor Profiling and Biomarker-Guided Therapy are Feasible
CHICAGO—A massive French database study shows that genetic tumor profiling in patients with non–small-cell lung cancer (NSCLC) is feasible, and is already helping physicians guide treatment in many patients, according to results presented at the American Society of Clinical Oncology annual meeting.

Analysis of the Biomarker France project was presented by Fabrice Barlesi, MD, PhD, of Aix-Marseille University. The project so far includes six markers: EGFR, KRAS, ALK, BRAF, HER2, and PI3K. The results were based on the first 10,000 patients included in the database, with 9,911 total samples included; 12 were excluded because another kind of solid tumor was found, and researchers were unable to identify the patient in 77 cases.

The included patients were 64% male and had an average age of 64.5 years; 38.1% were current smokers, 44.2% were former smokers, and 17.7% had never smoked. More than 70% had an ECOG performance status of 0 or 1. “In approximately 46% of the cases, a molecular alteration was seen,” Dr. Barlesi said.

The most common such alteration was KRAS mutation, in 27% of patients. EGFR activating mutation was seen in 9.5%, 0.8% had EGFR-resistant mutation, 0.9% had a HER2 mutation, 1.7% had BRAF mutation, 2.6% had PI3K mutation, and ALK rearrangement was seen in 3.7% of patients.

Dr. Barlesi said there was a large difference seen between those who were current or former smokers and those who had never smoked, as would be expected. Never-smokers had some alteration 65% of the time vs 45% of smokers; KRAS mutation was most common in smokers (31.7%) whereas EGFR activating mutation was seen most often in never-smokers (33.2%).

Notably, physicians used the results of tumor profiling to guide their first-line treatment decisions in 57% of evaluable cases. For example, in the 1,006 EGFR-mutated patients, 55.9% received an EGFR-targeted tyrosine kinase inhibitor. Among the 141 ALK-translocated patients, 69.8% received chemotherapy with pemetrexed(Drug information on pemetrexed) as first-line treatment.

Dr. Barlesi said that the median overall survival was 11.4 months, but that this was “very preliminary” data in only 2,250 evaluable patients. “The database is continuing to grow, and the final cohort will contain around 19,000 biomarker analyses,” he said. “This study shows that NSCLC tumor profiling is feasible.”

Lecia V. Sequist, MD, MPH, was the discussant for the session and added that newer biomarkers should be added to the database as it grows; she cited ROS1 in particular given recent research on that marker. Furthermore, Dr. Sequist noted that “genotyping needs to go hand in hand with efforts to increase availability to clinical trials.”

Pfizer Oncology Data Presentations at ASCO 2013.PDF (28.3 KB, 下载次数: 14)

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Abstract Number:
8039

Citation:
J Clin Oncol 31, 2013 (suppl; abstr 8039)

Author(s):
Tom Stinchcombe, Lynette M. Sholl, Xiaofei F. Wang, Lin Gu, Mark A. Socinski, Scott J. Rodig, Marzia Capelletti, Jeffrey Crawford, Martin J. Edelman, Miguel Angel Villalona-Calero, Robert Arthur Kratzke, Everett E. Vokes, Vincent A. Miller, Pasi Antero Janne, Alliance; The University of North Carolina at Chapel Hill, Chapel Hill, NC; Dana-Farber Cancer Institute/Brigham and Women’s Hospital, Boston, MA; Cancer and Leukemia Group B Statistical Center, Durham, NC; University of Pittsburgh Medical Center, UPMC Cancer Pavilion, Pittsburgh, PA; Department of Pathology, Division of Hematopathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Dana-Farber Cancer Institute, Boston, MA; Duke University Medical Center, Durham, NC; University of Maryland, Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD; The Ohio State University Wexner Medical Center, Columbus, OH; University of Minnesota, Minneapolis, MN; The University of Chicago Medicine and Biological Sciences, Chicago, IL; Foundation Medicine, Inc., Cambridge, MA



Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures

Abstract:


Background: CALGB (Alliance) 30406 was a randomized phase II trial that investigated erlotinib alone or in combination with carboplatin and paclitaxel in patients (pts) with a never or light smoking history with advanced NSCLC. Tissue collection was mandatory. Methods: Between August 2005 and April 2009 188 pts were enrolled. Tumor specimens were assessed using ALK immunohistiochemistry (IHC; clone D5F3; Cell Signaling); KRAS and HER2 mutations were tested. Results: The rate of mutations was: KRAS 10% (17/164), HER2 2% (3/164), and ALK + 7% (8/114). Given the small numbers of KRAS, HER2 and ALK positives, the analysis combines data from both arms. Pts with ALK + compared to ALK- NSCLC had an inferior ORR and PFS (Table). No statistically significant differences in ORR, PFS, OS between pts with KRAS or HER2 mutant and wild-type NSCLC were observed. In multivariate analysis pts with ALK+ compared to ALK- tumors experienced a statistically significant worse PFS (HR=2.67, p=0.0114) but not OS (HR=1.48, p=0.3217). One pt was identified as having an EGFR exon 21 mutation and ALK +; the pt experienced a best response of progressive disease, a PFS of 2.9 months, and OS of 17.4 months. Conclusions: (1) Pts with ALK+ compared to ALK- NSCLC have a lower ORR, worse PFS, but not OS with erlotinib alone or with carboplatin and paclitaxel. (2) The prevalence ALK+, KRAS and HER2 mutations observed was 7%, 10% and 2%, respectively. Clinical trial information: 00126581.