Journal Thoracic Oncology

Recommendations

Info

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017 POSTER SESSION 2 – P2.03A: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/ IMMUNOTHERAPY CLINICAL TRIALS – TUESDAY, DECEMBER 6, 2016 P2.03A-007 PEM/CBP/BEV FOLLOWED BY PEM/BEV IN HISPANIC PATIENTS WITH NSCLC: OUTCOMES ACCORDING TO COMBINED SCORE OF TS, ERCC1 AND VEGF EXPRESSION Andrés Cardona 1 , Leonardo Rojas 2 , Beatriz Wills 3 , Oscar Arrieta 4 , Hernan Carranza 1 , Carlos Vargas 1 , Jorge Otero 1 , Mauricio Cuello 5 , Luis Corrales 6 , Claudio Martin 7 , Carlos Ortiz 1 , Sandra Franco 1 , Rafael Rosell 8 1 Medical Oncology, Clinical and Traslational Oncology Group, Institute of Oncology, Clínica Del Country, Bogota/Colombia, 2 Centro Javeriano de Oncología, Hospital Universitario San Ignacio, Bogotá/Colombia, 3 Internal Medicine Department, Johns Hopkins Hospital, Baltimore, Maryland/United States of America, 4 Thoracic Oncology Unit and Laboratory of Personalized Medicine, Instituto Nacional de Cancerologia, Mexico City/Mexico, 5 Medical Oncology Department, Udelar (Montevideo, Uruguay), Montevideo/Uruguay, 6 Clinical Oncology Department, Hospital San Juan de Dios (San José, Costa Rica), San Jose/Costa Rica, 7 Department of Clinical Oncology, Instituto Alexander Fleming, Buenos Aires/Argentina, 8 Hospital Germans Trias I Pujol, Catalan Institute of Oncology, Barcelona/Spain Background: To evaluate the efficacy and safety of pemetrexed, carboplatin and bevacizumab (PCB) followed by maintenance pemetrexed and bevacizumab (PB) in chemotherapy-naïve patients with stage IV nonsquamous non-small cell lung cancer (NSCLC) through the influence of thymidylate synthase (TS), ERCC1 and VEGF mRNA expression on several outcomes. The primary endpoints were the overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). Methods: Patients were administered pemetrexed (500 mg/m2), carboplatin (AUC, 5.0 mg/ml/ min) and bevacizumab (7.5 mg/kg) intravenously every three weeks for up to four cycles. Maintenance pemetrexed and bevacizumab was administered until disease progression or unacceptable toxicity. Results: One hundred forty-four Hispanic patients with a median follow-up of 13.8 months and a median number of maintenance cycles of 6 (range, 1- 32) were assessed. The ORR among the patients was 66% (95% CI, 47% to 79%). The median progression-free and overall survival (OS) rates were 7.9 months (95% CI, 5.9-10.0 months) and 21.4 months (95% CI, 18.3 to 24.4 months), respectively. Median TS, ERCC1 and VEGF mRNA levels were 1.45 (range, 0.17–2.52), 0.58 (range, 0.44-1.20), and 2.72 (range, 1.84-3.21), respectively. OS was significantly higher in patients with the lowest TS mRNA levels [29.6 months (95%CI 26.2-32.9) compared with those with higher levels 9.3 months (95%CI 6.6-12.0); p=0.0001]. ERCC1 mRNA levels also influenced the OS [median for ERCC1 mRNA˂0.58 28.7 months (95%CI 26.3-31.2) vs. ERCC1 mRNA>0.58 11.1 months (95%CI 9.6-12.7); p=0.0001] as well as VEGF mRNA levels [median OS for VEGF mRNA˂2.72 26.4 months (95%CI 22.8-30.0) vs. VEGF mRNA>2.72 18.2 months (95%CI 8.4-27.9); p=0.009]. TS mRNA did not influence treatment response, however the ORR was significantly higher in patients with low levels of ERCC1 (p = 0.003) and elevated VEGF (p = 0.005). Multivariate analysis found that TS mRNA levels (p=0.0001), VEGF mRNA levels (p=0.007) and PS (p=0.014) were independent prognostic factors. Conclusion: Overall, PCB followed by maintenance pemetrexed and bevacizumab was in Hispanic patients with non-squamous NSCLC. This regimen was associated with prolonged OS, particularly in patients with low TS, ERCC1 and VEGF mRNA expression. These biomarkers alone or in combination may be useful to assess the prognosis of patients with NSCLC treated with CBP/Pem/Bev. Keywords: Pemetrexed/carboplatin/bevacizumab, Maintenance pemetrexed/ bevacizumab, Hispanic patients, TS, ERCC1 and VEGF expression oncology practice setting. Methods: This was a retrospective study using the McKesson Specialty Health/US Oncology iKnowMed SM electronic health record database. Inclusion criteria: Patients with advanced (stage III/IV) NSCLC who initiated first-line, intravenous, myelosuppressive chemotherapy between January 2007 and December 2010. Endpoints: Mean RDI (a composite measure including both dose delays and dose reductions), RDI
Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017 disease and a limited number of metastatic lesions (≤5) per organ site and a limited number of affected organ sites (1 or 2) were eligible. Results: Eighteen patients were identified for analysis during the study period. The most frequent metastatic site was the central nervous system (CNS, 72%). Most patients (83%) received systemic chemotherapy, with only three (17%) undergoing aggressive surgery, for the primary lung tumor. The CNS failure sites for patients with CNS metastases were located outside of the surgery or radiosurgery field. The median OS for all patients was 15.9 months, with that for EGFR mutation–positive patients tending to be longer than that for EGFR mutation–negative patients. Conclusion: Our results indicate that a cure is difficult to achieve with current treatment strategies for NSCLC patients with synchronous oligometastases, although a few long-term survivors and a smaller number of patients alive at last follow-up were present among the study cohort. There is an urgent clinical need for prospective evaluation of surgical resection as a treatment for oligometastatic NSCLC negative for driver mutations. Keywords: oligometastatisis, non–small cell lung cancer, chemotherapy POSTER SESSION 2 – P2.03A: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/ IMMUNOTHERAPY CLINICAL TRIALS – TUESDAY, DECEMBER 6, 2016 P2.03A-010 A RANDOMIZED PHASE II STUDY OF PLATINUM-BASED CHEMOTHERAPY +/- METFORMIN IN CHEMOTHERAPY-NAÏVE ADVANCED NON-SQUAMOUS NSCLC Kristen Marrone 1 , Patrick Forde 1 , Julie Brahmer 1 , Gary Rosner 2 , Xian Zhou 2 , Barbara Coleman 1 , David Ettinger 1 1 Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore/MD/ United States of America, 2 Biostatistics, Johns Hopkins University, Baltimore/MD/ United States of America Background: Lung cancer is the number one cause of cancer-related death. 80% of patients present with advanced disease, and first line standard of care is multi-agent chemotherapy; however, overall 2-year survival is only 15%. Metformin, a well-tolerated oral biguanide used in diabetes, is thought to have anti-cancer effects via a variety of proposed mechanisms. Methods: This is a single-arm study with a randomized control arm for reference to expected 1-year progression-free survival (PFS), the primary endpoint, defined as the proportion of patients alive without disease progression at 1 year of treatment. Non-diabetic, chemotherapy-naïve patients with advanced non-squamous NSCLC were randomized 3:1 to Arm A:Arm B. (NCT01578551) Arm A consisted of standard doses of paclitaxel, carboplatin, bevacizumab (PCB) and metformin (M; 1,000 mg PO BID) x 4-6 cycles, followed by bevacizumab (B) + M until disease progression. Arm B consisted of standard doses of PCB x 4-6 cycles, followed by B until disease progression. Results: The study enrolled 19 patients to Arm A and 6 patients to Arm B. 37% of Arm A patients and 33% of Arm B patients were male. Median age was 58 years (range: 37-64) in Arm A and 64 years (range: 55-70) in Arm B. One-year PFS for Arm A was 0.47 (95% CI: 0.25, 0.88). The 95% CI lower bound exceeded 15%, the hypothesized 1-year PFS without metformin. All Arm B patients either progressed or were off study treatment prior to 1 year. Median PFS (Figure) was statistically significantly better for Arm A patients (9.6 months; 95% CI: 7.3 months, Not Reached (NR)) than Arm B patients (6.7 months; 95% CI: 4.4 months, NR). POSTER SESSION 2 – P2.03A: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/ IMMUNOTHERAPY CLINICAL TRIALS – TUESDAY, DECEMBER 6, 2016 P2.03A-011 POPULATION PHARMACOKINETIC/ PHARMACODYNAMIC MONITORING OF PEMETREXED TO PREDICT SURVIVAL IN PATIENTS WITH ADVANCED NSCLC Sabine Visser 1 , Stijn Koolen 2 , Marcel Stoop 3 , Theo Luider 3 , Ron Mathijssen 2 , Bruno Stricker 4 , Joachim Aerts 1 1 Pulmonary Medicine, Erasmus MC Cancer Institute, Rotterdam/Netherlands, 2 Internal Oncology, Erasmus MC Cancer Institute, Rotterdam/Netherlands, 3 Neurology, Erasmus MC, Rotterdam/Netherlands, 4 Epidemiology, Erasmus MC, Rotterdam/Netherlands Background: A major challenge in advanced non-small cell lung cancer (NSCLC) remains the identification of predictors of clinical benefit from pemetrexed. Total systemic exposure to pemetrexed and its metabolites could be predictive for progression-free and overall survival (PFS/OS). However, sampling times in population pharmacokinetic (PK) analyses of pemetrexed are limited. We performed population PK modeling of pemetrexed during total treatment period and evaluated total systemic exposure as a predictor. Methods: In a prospective observational multi-center study, treatmentnaive patients with stage IIIB or IV NSCLC receiving pemetrexed/platinum treatment were enrolled. Pemetrexed, dosed based on body surface area (500mg/m 2 ), was administered as a 10-minute intravenous infusion every 21 days. Prior to and weekly after each pemetrexed administration, plasma sampling was performed (cycle-PK). Simultaneously, glomerular filtration rate (GFR) was estimated using the Chronic Kidney Disease Epidemiology Collaboriation (CKD-EPI) formula. In a subgroup, blood samples were collected at 10, 30 minutes and 1,2,4, 8, 24 hours after start of pemetrexed infusion (24-hour-PK). We used a recently validated assay to quantify plasma pemetrexed concentrations (Stoop et al, J Pharm Biomed Anal 2016;128:1- 8). Population PK analyses were performed using nonlinear mixed effects modeling (NONMEM version 7.2). The final model, based on both cycle-PK and 24-hour-PK, was used to estimate the area under the plasma concentration versus time curve during cycle 1 (AUC cycle ). With a Cox-regression analysis we examined the relation between AUC cycle and OS/PFS, adjusted for known prognostic factors (sex, disease stage, WHO performance-score). Results: For 97 of the 151 patients, concentrations of pemetrexed were quantified (24-hour-PK, n=15; cycle-PK, n=82). A two-compartment model parametrized (population estimate (%standard error of the estimate) in terms of clearance (CL; 5.44L/h (14.9%)), central distribution volume (V 1 ; 19.6L (11.3%)), peripheral distribution volume (V 2 ; 173L (32.7%)), intercompartimental clearance (Q; 0.19L/h (31.6%)) and incorporated between-patient variability of CL (10.7%), estimated cycle-PK appropriately. GFR and other covariates did not improve the estimation of the parameters. The AUC cylce was significantly different between males (190.8±64.9mg·h/L) and females (165.4±47.2mg·h/L). When we stratified for sex, the highest quartile of AUC independently predicted worse OS (HR=3.06, 95%CI: 1.43-6.57) and PFS (HR=2.79 95%CI: 1.36-5.70), adjusted for the remaining prognostic factors, GFR and pemetrexed dosage. Conclusion: Paradoxically worse OS and PFS in patients with high plasma pemetrexed AUC may suggest lower intracellular levels of pemetrexed. Another possibility is that these patients poorly metabolize pemetrexed into its more effective metabolites, which inhibit tumor growth more strongly by prolonged intracellular retention and higher affinity to target enzymes. Keywords: pemetrexed, advanced NSCLC, overall survival, PK/PD analysis POSTER SESSION 2 – P2.03A: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/ IMMUNOTHERAPY CLINICAL TRIALS – TUESDAY, DECEMBER 6, 2016 P2.03A-012 NEPHROTOXICITY IN PATIENTS WITH ADVANCED NSCLC RECEIVING PEMETREXED-BASED CHEMOTHERAPY Sabine Visser 1 , Jeannine Huisbrink 2 , Jermo Van Toor 1 , Nico Van Walree 3 , Bruno Stricker 4 , Joachim Aerts 1 1 Pulmonary Medicine, Erasmus MC Cancer Institute, Rotterdam/Netherlands, 2 Pharmacy, Franciscus Gasthuis En Vlietland, Rotterdam/Netherlands, 3 Amphia Hospital, Breda/Netherlands, 4 Epidemiology, Erasmus MC, Rotterdam/Netherlands Conclusion: The addition of metformin to standard first-line PCB was well-tolerated and significantly improves PFS in chemotherapy-naïve advanced non-squamous NSCLC patients. Further study of the addition of metformin to treatment in NSCLC patients is needed. Keywords: chemotherapy, metformin, non-small cell lung cancer Background: In patients with advanced non-small cell lung cancer (NSCLC) pemetrexed (PEM) is increasingly used as maintenance therapy after induction PEM/platinum treatment. Despite the extensive use of PEM, the incidence of nephrotoxicity during (maintenance) PEM therapy has not been systematically evaluated. Knowledge about nephrotoxicity during PEM-based treatment could determine the need for adapted renal protective strategies. We assessed the occurrence of nephrotoxicity and its influence on treatment continuation in NSCLC patients receiving PEM-based therapy. Methods: In a prospective observational multi-center study, treatment-naive patients with stage IIIB or IV NSCLC were enrolled. Patients were treated with PEM-cisplatin Copyright © 2016 by the International Association for the Study of Lung Cancer S467
Page 1 and 2:
Volume 12 • Issue S1 • January
Page 3 and 4:
Abstracts Journal of Thoracic Oncol
Page 5 and 6:
Page 7 and 8:
Page 9 and 10:
Page 11 and 12:
Page 13 and 14:
Page 15 and 16:
Page 17 and 18:
Page 19 and 20:
Page 21 and 22:
Page 23 and 24:
Page 25 and 26:
Page 27 and 28:
Page 29 and 30:
Page 31 and 32:
Page 33 and 34:
Page 35 and 36:
Page 37 and 38:
Page 39 and 40:
Page 41 and 42:
Page 43 and 44:
Page 45 and 46:
Page 47 and 48:
Page 49 and 50:
Page 51 and 52:
Page 53 and 54:
Page 55 and 56:
Page 57 and 58:
Page 59 and 60:
Page 61 and 62:
Page 63 and 64:
Page 65 and 66:
Page 67 and 68:
Page 69 and 70:
Page 71 and 72:
Page 73 and 74:
Page 75 and 76:
Page 77 and 78:
Page 79 and 80:
Page 81 and 82:
Page 83 and 84:
Page 85 and 86:
Page 87 and 88:
Page 89 and 90:
Page 91 and 92:
Page 93 and 94:
Page 95 and 96:
Page 97 and 98:
Page 99 and 100:
Page 101 and 102:
Page 103 and 104:
Page 105 and 106:
Page 107 and 108:
Page 109 and 110:
Page 111 and 112:
Page 113 and 114:
Page 115 and 116:
Page 117 and 118:
Page 119 and 120:
Page 121 and 122:
Page 123 and 124:
Page 125 and 126:
Page 127 and 128:
Page 129 and 130:
Page 131 and 132:
Page 133 and 134:
Page 135 and 136:
Page 137 and 138:
Page 139 and 140:
Page 141 and 142:
Page 143 and 144:
Page 145 and 146:
Page 147 and 148:
Page 149 and 150:
Page 151 and 152:
Page 153 and 154:
Page 155 and 156:
Page 157 and 158:
Page 159 and 160:
Page 161 and 162:
Page 163 and 164:
Page 165 and 166:
Page 167 and 168:
Page 169 and 170:
Page 171 and 172:
Page 173 and 174:
Page 175 and 176:
Page 177 and 178:
Page 179 and 180:
Page 181 and 182:
Page 183 and 184:
Page 185 and 186:
Page 187 and 188:
Page 189 and 190:
Page 191 and 192:
Page 193 and 194:
Page 195 and 196:
Page 197 and 198:
Page 199 and 200:
Page 201 and 202:
Page 203 and 204:
Page 205 and 206:
Page 207 and 208:
Page 209 and 210:
Page 211 and 212:
Page 213 and 214:
Page 215 and 216:
Page 217 and 218:
Page 219 and 220:
Page 221 and 222:
Page 223 and 224:
Page 225 and 226:
Page 227 and 228:
Page 229 and 230:
Page 231 and 232:
Page 233 and 234:
Page 235 and 236:
Page 237 and 238:
Page 239 and 240:
Page 241 and 242:
Page 243 and 244:
Page 245 and 246:
Page 247 and 248:
Page 249 and 250:
Page 251 and 252:
Page 253 and 254:
Page 255 and 256:
Page 257 and 258:
Page 259 and 260:
Page 261 and 262:
Page 263 and 264:
Page 265 and 266:
Page 267 and 268:
Page 269 and 270:
Page 271 and 272:
Page 273 and 274:
Page 275 and 276:
Page 277 and 278:
Page 279 and 280:
Page 281 and 282:
Page 283 and 284:
Page 285 and 286:
Page 287 and 288:
Page 289 and 290:
Page 291 and 292:
Page 293 and 294:
Page 295 and 296:
Page 297 and 298:
Page 299 and 300:
Page 301 and 302:
Page 303 and 304:
Page 305 and 306:
Page 307 and 308:
Page 309 and 310:
Page 311 and 312:
Page 313 and 314:
Page 315 and 316:
Page 317 and 318:
Page 319 and 320:
Page 321 and 322:
Page 323 and 324:
Page 325 and 326:
Page 327 and 328:
Page 329 and 330:
Page 331 and 332:
Page 333 and 334:
Page 335 and 336:
Page 337 and 338:
Page 339 and 340:
Page 341 and 342:
Page 343 and 344:
Page 345 and 346:
Page 347 and 348:
Page 349 and 350:
Page 351 and 352:
Page 353 and 354:
Page 355 and 356:
Page 357 and 358:
Page 359 and 360:
Page 361 and 362:
Page 363 and 364:
Page 365 and 366:
Page 367 and 368:
Page 369 and 370:
Page 371 and 372:
Page 373 and 374:
Page 375 and 376:
Page 377 and 378:
Page 379 and 380:
Page 381 and 382:
Page 383 and 384:
Page 385 and 386:
Page 387 and 388:
Page 389 and 390:
Page 391 and 392:
Page 393 and 394:
Page 395 and 396:
Page 397 and 398:
Page 399 and 400:
Page 401 and 402:
Page 403 and 404:
Page 405 and 406:
Page 407 and 408:
Page 409 and 410:
Page 411 and 412:
Page 413 and 414:
Page 415 and 416:
Page 417 and 418: Abstracts Journal of Thoracic Oncol
Page 467: Abstracts Journal of Thoracic Oncol
Page 519 and 520:
Page 521 and 522:
Page 523 and 524:
Page 525 and 526:
Page 527 and 528:
Page 529 and 530:
Page 531 and 532:
Page 533 and 534:
Page 535 and 536:
Page 537 and 538:
Page 539 and 540:
Page 541 and 542:
Page 543 and 544:
Page 545 and 546:
Page 547 and 548:
Page 549 and 550:
Page 551 and 552:
Page 553 and 554:
Page 555 and 556:
Page 557 and 558:
Page 559 and 560:
Page 561 and 562:
Page 563 and 564:
Page 565 and 566:
Page 567 and 568:
Page 569 and 570:
Page 571 and 572:
Page 573 and 574:
Page 575 and 576:
Page 577 and 578:
Page 579 and 580:
Page 581 and 582:
Page 583 and 584:
Page 585 and 586:
Page 587 and 588:
Page 589 and 590:
Page 591 and 592:
Page 593 and 594:
Page 595 and 596:
Page 597 and 598:
Page 599 and 600:
Page 601 and 602:
Page 603 and 604:
Page 605 and 606:
Page 607 and 608:
Page 609 and 610:
Page 611 and 612:
Page 613 and 614:
Page 615 and 616:
Page 617 and 618:
Page 619 and 620:
Page 621 and 622:
Page 623 and 624:
Page 625 and 626:
Page 627 and 628:
Page 629 and 630:
Page 631 and 632:
Page 633 and 634:
Page 635 and 636:
Page 637 and 638:
Page 639 and 640:
Page 641 and 642:
Page 643 and 644:
Page 645 and 646:
Page 647 and 648:
Page 649 and 650:
Page 651 and 652:
Page 653 and 654:
Page 655 and 656:
Page 657 and 658:
Page 659 and 660:
Page 661 and 662:
Page 663 and 664:
Page 665 and 666:
Page 667 and 668:
Page 669 and 670:
Page 671 and 672:
Page 673 and 674:
Page 675 and 676:
Page 677 and 678:
Page 679 and 680:
Page 681 and 682:
Page 683 and 684:
Page 685 and 686:
Page 687 and 688:
Page 689 and 690:
Page 691 and 692:
Page 693 and 694:
Page 695 and 696:
Page 697 and 698:
Page 699 and 700:
Page 701 and 702:
Page 703 and 704:
Page 705 and 706:
Page 707 and 708:
Page 709 and 710:
Page 711 and 712:
Page 713 and 714:
Page 715 and 716:
Page 717 and 718:
Page 719 and 720:
Page 721 and 722:
Page 723 and 724:
Page 725 and 726:
Page 727 and 728:
Page 729 and 730:
Page 731 and 732:
Page 733 and 734:
Page 735 and 736:
Page 737 and 738:
Page 739 and 740:
Page 741 and 742:
Page 743 and 744:
Page 745 and 746:
Page 747 and 748:
Page 749 and 750:
Page 751 and 752:
Page 753 and 754:
Page 755 and 756:
Page 757 and 758:
Page 759 and 760:
Page 761 and 762:
Page 763 and 764:
Page 765 and 766:
Page 767 and 768:
Page 769 and 770:
Page 771 and 772:
Page 773 and 774:
Page 775 and 776:
Page 777 and 778:
Page 779 and 780:
Page 781 and 782:
Page 783 and 784:
Page 785 and 786:
Page 787 and 788:
Page 789 and 790:
Page 791 and 792:
Page 793 and 794:
Page 795 and 796:
Page 797 and 798:
Page 799 and 800:
Page 801 and 802:
Page 803 and 804:
Page 805 and 806:
Page 807 and 808:
Page 809 and 810:
Page 811 and 812:
Page 813 and 814:
Page 815 and 816:
Page 817 and 818:
Page 819 and 820:
Page 821 and 822:
Page 823 and 824:
Page 825 and 826:
Page 827 and 828:
Page 829 and 830:
Page 831 and 832:
Page 833 and 834:
Page 835 and 836:
Page 837 and 838:
Page 839 and 840:
Page 841 and 842:
Page 843 and 844:
Page 845 and 846:
Page 847 and 848:
Page 849 and 850:
Page 851 and 852:
Page 853 and 854:
Page 855 and 856:
Page 857 and 858:
Page 859 and 860:
Page 861 and 862:
Page 863 and 864:
Page 865 and 866:
Page 867 and 868:
Page 869 and 870:
Page 871 and 872:
Page 873 and 874:
Page 875 and 876:
Page 877 and 878:
Page 879 and 880:
Page 881 and 882:
Page 883 and 884:
Page 885 and 886:
Page 887 and 888:
Page 889 and 890:
Page 891 and 892:
Page 893 and 894:
Page 895 and 896:
Page 897 and 898:
Page 899 and 900:
Page 901 and 902:
Page 903 and 904:
Page 905:
Page 912:
LILLY ONCOLOGY IS DEDICATED TO ADVA
show all

Journal Thoracic Oncology

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?