Volume 33. Issue 158. Part | of II
`
`ONCOLOGY
`
`Official Journal of the
`American Society of Clinical Oncology
`
`Journal of clinical oncology : official JOU'T‘la' 0f the
`An'ierican Society of" Clinical Dncology’.
`M’-
`no.15_,. aiiool. ol.l [2015}
`Go
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`Wl JC158‘94H
`
`‘ 2015 ASCO Annual Meeting Proceedings
`
`JOURNAL OF
`CLINICAL
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`ASCQ/fl
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`PROPERTY OF THE
`NATIONAL
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`Slst Annual Meeting
`May 29-June 2, 2015
`McCormick Place
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`PGR2019-00002
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`Editor: Michael A. Carducci, MD
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`Managing Editor: Amy Hindrnan
`Editorial Coordinator: Devon Carter
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`Editorial Assistant: Hilary Adams
`Production Manager: Donna Dottellis
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`mechanical. Including photocopy, recording,
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`CLINICAL
`
`\.I*I:-,I|III-ne 33r ISSUQ 155
`
`Supplement to May 20, 2015
`
`ONCOLOGY~_,_»M
`
`CONTENTS
`
`2015 ASCO ANNUAL MEETING PROCEEDINGS
`
`Special Award Lecture Abstracts
`
`Plenary Session
`(Abstracts LIN-H
`[RAM
`Pathways Clinical Science 5'r\""‘F""5ia
`(Abstracts Li’iAlOO - LBMOQI
`
`Global Oncoloqv Symposium
`(Abstract 200)
`
`Breast Cancer-HERZI’ER
`Schedu ed prosemtatlons (Abslracls 500 - TF’S642)
`Breast Cancer-Triple-Neqative/Cytotoxics/Local Therapy
`Sta-“"3“ 9d pmsentations (Abstracts 1000 -TPS11|3)
`Cancer Prevention, Genetics, and Epidemi°l°QY
`Schedu ed presentations {Abstracts 1.500
`1592)
`
`Cantral Nervous System Tumors
`Slihé‘rlu ed prom-minnow; (Abstracts 2000 - 113552081)
`DEVEIODmentaI Therapeutics-Clinical Pharmacolqu 3"“ Experimental Therapeutics
`Sthedu 9(1 pregame-Ilium (Abstracts 2.500 - TF’S2624}
`Deveiopmental Therapeutics-lmmunotheraPY
`Scheclu 0d [Jresentalions (Abstracts 3000 TP53105}
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`This material may be protected by capyr'um law (Title 17 u.s. Code]
`
`
`
`4005
`
`7500
`
`Bevacizumab lSmgikg plus cisplatin-pemetrexed (CP) triplet versus CP
`doublet in Malignant Pleural Mesothelioma (MPM): Results of the IFCT-
`GFPC-07D l MAPS randomized phase 3 trial. First Author: Gerard Zaicrrian.
`Caeii Univ Hosp. Caren, France
`Background: MPM median overall survival (03) did not exceed 13 months
`with pemetrexed-plalinum doublet. with virtually no surviving patients at 5
`years. Vascular endothelial growth factor is a potent milogen for MPM cells.
`Methods:
`in this French inulticenler randomized phase 3 trial. eligible
`patients had unresectable. histologically proved MPM. age
`1'6, no prior
`chemo. PS 02. no thrombosis. nor bleeding. Randomized patients (1:1)
`received pem 500 mgim'“. CDDP i5 mgi'm? at D1. with (arm B) or Without
`bevacizumab (arm A). 15 mgikg 0210. for 6 cycles. Arm 8 non-progressive
`patients received bevacizumab maintenance therapy until progression or
`toxicity. Primary endpoint was US. 445 patients were to be randomized.
`and 385 events observed. to show a significant 05 improvement. with 80%
`statistical power. 5% a-risk. Results: From Feb. 2008 to Jan. 2014. 448
`patients were included in 73 centers. Males.- 75.4%. median age.- 65.7
`years (range 34.1-15.9). PS 0-1: 96.7%. The IDMC recommended a
`second interim analysis after 85% of events. On 01—Jan—20 l 5. the duration
`since last news was *- 30 days in 105 out of 106 still
`living patients.
`Overall survival was significantly longer in the experimental arm (median:
`18.8 months, 95%CII15.9-22.6l vs. 16.1 months. 95%Clll4.0-17.9l for
`the reference arm. (adj.HR = 0.76. 959600061: 0.94]. p = 0.012). With
`only 46i448 non-progressive patients at the date of analysis. median PFS
`was 9.6 months. 9553011851061 in bevacizumab arm vs. 7.5 months.
`95%Cll6.8—8.ll (adi.HR = 0.62. 95%CI10.50-0.75l. p -'-' 0.0001). 63-4
`hematological toxicities did not significantly differ in the two arms (49.5%
`vs. 413%). Significantly more (33 proteinuria (0.0 vs. 3. 1%). G3 hyperten-
`sion (0.0 vs. 23%). 03-4 arterial thrombotic events (0.0 vs. 2.11%) were
`observed in bevacizumab arm. 00L and exploratory biomarkers studies will
`be also presented at
`time of
`the meeting. Conclusions: Bevacizumab
`addition to pemetrexedicis—platin provides a significantly longer survival in
`pts with MPM. with acceptable toxicity. making this triplet a new treatment
`paradigm. Clinical trial information: NCT00651456.
`
`Oral ilbsuact Session. Sat. 3:00 Fifi-5:00 PM
`7502
`Pembrolizumob (MK-3475) in patients (pts) with extensive-stage small cell
`lung cancer (SCLC): Preliminary safety and efficacy results from KEYNOTE-
`023. First Author: Patrick Aiexander Off, Dana-Farber Cancer institute.
`Boston. MA
`
`Background: Treatment options for pts with SCLC that progresses on
`platinum—based chemotherapy are limited. Pembrolizumab. an anti-'PD-l
`monoclonal antibody designed to block the interaction between PD-l and
`its ligands PD-Ll and PD—L2. has shown antitumor activity in multiple
`advanced malignancies. including non—small cell lung cancer. We assessed
`the safety and efficacy of pembrolizumab in pts with PD—Ll ' SCLC.
`Methods: KEYNOTE-028 (ClinicalTrialsgov. NCT02054806) is an ongoing
`multicohort. phase lb study of pembrolizumab in pts with PD-Ll'
`advanced solid tumors. Key eligibility criteria for the SCLC cohort include:
`confirmed. measurable disease; PD-Ll expression in —_=- 1% of cells in
`tumor nests or PD-Ll ’ bands in stroma as assessed by IHC at a central
`laboratory; failure of standard therapy; and absence of autoimmune disease
`or interstitial lung disease. Pembrolizumab 10 mgikg is given every 2 wk for
`up to 2 y or until confirmed progression or unacceptable toxicity. Primary
`end points are safely. tolerabiiity. and response assessed per RECIST v1.1
`by investigator review every 8 wk for the first 6 mo and every 12 wk
`thereafter. Results: Of the 135 pts with SCLC screened. 37 (27%) had
`PD-Lll
`tumors. Seventeen pts were enrolled from March 2014 through
`January 2015 (59% men.- median age. 62 y: 59% E000 PS 1). One pt was
`misenrolled and did not receive pembrolizumab. All 16 treated pts received
`prior platinum and etoposide. 9 pts (53%) experienced a drug—related AE
`(DRAE): only 1 pt had a grade 2 3 DRAE. There were no treatment-related
`deaths or discontinuations due to DRAEs. Four of 16 (25%) evaluable pts
`had a partial response. One (7%) pt had stable disease. resulting in a
`disease control rate of 31%. Six (37%) pts had progressive disease as their
`best response. and 5 pts had no assessment at
`the time of analysrs.
`Responses are durable. with all responders on treatment for 16 -i wks with
`ongoing rest-rouse. Conclusions: Pembrolizumab is generally well tolerated
`and has promising antitumor activity in pts with PD-Ll ‘ SCLC who have
`progressed on prior platinum-based therapy. Enrollment in the SCLC cohort
`of KEYNOTEAOEB is ongoing. Clinical trial information: NCT02054806.
`
`Lung ConcereNon-Smoii Ceii Locoi-Regionoi/Smoli Cali/Other Thoracic Cancers
`
`Oral ilhstract Session. Sat. 3:00 PM-E:00 PM
`
`0ral Abstract Session. Sat. 3:00 PM-6:00 PM
`‘i‘50l
`Phase III trial (NGROIS) with NGR~hTNF plus best investigator choice
`(BIC) versus placebo plus BIC in previously treated patients with advanced
`malignant pleural mesothelioma (MPM). First Author: Rehab M. Gaafar.
`National Cancer institute. Cairo University. Cairo. Egypt
`Background: Currently. there are no standard options for MPlv‘l patients who
`failed a pemetrexed-based chemotherapy (CT). NGR-hTNF. a
`tumor-
`targeted antivascular agent. displays antitumor activity through a vessel
`normalization that improves intratunior CT uptake and T—cell
`infiltration.
`Methods: MPM patients who progressed on or after a front—line pemetrexed—
`based regimen. stratified for performance status (PS) and CT agent. were
`randomly assigned to receive weekly NGR—hTNF 0.8 pgimp (arm it. n -
`200) or placebo (arm 8: n ; 200). both given with BIC lgcmcitabine (G1.
`yinorelbine W]. dottorubicin iDI or supportive care). Primary endpoint was
`overall survival (05). Hypothesis testing: hazard ratio (HR) = 0.72. 1-0 =
`0.80. n = 0.05. Results: Baseline characteristics were balanced between
`arms (A vs 8): median age (65 vs 67 years); men (76% vs 74%); PS 2 1
`(72% vs 69%).- nonepithelial histology (15% vs 19%); poor EORTC score
`(30% vs 23%): prior treatmentvfree interval (TFI) < median of 4.8 months
`(47% vs 53%). Investigator—selected CT (n —- 381. 95%): G 55%. v 42%.
`D 3%. Patients completing six CT cycles: 41% vs 32% (p = 0.08). Most
`common grade 3i4 toxicity: neutropenia (17% vs 19%) and fatigue (5% V5
`8%). After a median follow—up of 18.9 months. 03 did not differ
`significantly between arms in iTT analysis (median 8.4 vs 7.9 months: HR
`= 0.94 p = 0.61). By predefined OS analyses. there was a significant
`interaction only between treatment group and TFI (p = 0.008).
`in 198
`patients with TFI shorter than 4.8 months after first-line therapy. median
`08 for NGR—hTNF vs placebo was 9.0 vs 6.3 months and 1-year OS was
`39% vs 23%. respectively(HR 3- 0.69 p = 0.02; stratified HR = 0.65 p =
`0.01 ). By CT agent. median 08 for NGR—hTNF plus G vs placebo plus 0 was
`9.0 vs 6.2 months and for NGR-liTNF plus V vs placebo plus V was 9.? vs
`6.9 months. A significant treatment-by-TFI interaction was also observed
`for PFS (p = 0.009). with 6-month rates in the short TFl subset of 25% for
`NGR—hTNF and 12% for placebo (HR = 0.71 p = 0.03). Conclusions:
`Though the primary endpoint was not met. 08 and PFS benefit reported
`with NGR—hTNF plus CT in patients with short TFl deserves a confirmatory
`first-line phase III trial. Clinical trial information: NCT01098266.
`
`Oral Abstract Session. Sat. 3:00 Phil-5:00 PM
`7503
`Phase lill study of nivolumab with or without ipilimumab for treatment of
`recurrent small cell lung cancer (SCLC): (01209-032. First Author: Scott
`Joseph Antonia. Mottitt Cancer Center. Tampa. FL
`Bailllllround: Patients (pts) with SCLC respond to initial platinum (PLT)
`based chemotherap)r (CT). but rapidly progress. Combined blockade of
`Pill—1 and CTLA-4 immune checkpoint pathways has anti-tumor activity
`with a manageable safety profile. Nivolumab (Nl‘iiO) is a fully human lg04
`PD-l
`immune checkpoint inhibitor approved in the US 3- Japan. interim
`safety and efficacy of NlllO +\A ipilimumab (IPI). a CTLA—4 checkpoint
`inhibitor. in pretreated SCLC pts are reported. Methods: Pts who were PLT
`sensitive or refractory and had progressive disease were enrolled regardless
`of tumor PD—LI status or number of prior CT regimens. This open—label
`study randomized pts to NWO 3 mgikg IV 02W or NIVO+ IPI (1 + 1 mgikg.
`1 + 3 mgikg or3 + 1 mall-lg) llir 03W for4 cycles followed by NIVO3 mgikg
`02W. Primary objective was Overall response rate (ORR). Other objectives
`were safety. PFS. OS and biomarker analysis. Results: Seventy-five pts were
`enrolled (NIVO. n = 40; va0+IPL n = 35): 59% had 2 2 prior regimens.
`Drug-related adverse events (DrAEs)
`in e- 10% were fatigue (18%).
`diarrhea (13%). nausea (10%). and decreased appetite (10%) with NWO:
`and fatigue (29%). diarrhea (17%). pruritus (14%}. nausea. endocrine
`disorders and rash (11% each) with NIVOi-IPI. Gr 3i4 DrAE in _:_- 5%
`included diarrhea and rash (6% each; NlV0+ lPl). Drug-related pneumoni-
`tis occurred in 2 pts (1 per arm). One pt experienced a drug-related SAE of
`myasthenia gravis on study which was fatal. 0f 40 evaluable NWO pts.
`partial response (PR) was seen in 6. 15% (duration of ongoing responses
`[DORI 80-2511 days); stable disease (SD) in 9. 22.5%; and progressive
`disease (PD) in 25. 62.5%. in 20 evaluable NIVO-i lPl pts. 1 had complete
`response (CR). 5% (00R 322+ days): 4 had a PR. 20% (DOR 41-83+
`days); 6 had 80. 30%. and 9 had P0. 45%. In the NIVO+ lPI arm. 12 pts
`had not reached first tumor assessment and 3 were not evaluable. Nine 1315
`{23%) continue treatment with NlVO and 19 (54%) with Nlli0+lPL
`Conclusions:
`in this PD-Ll unselected SCLC population with progression
`post-FLT. NIVO alone or combined wilh lPl was tolerable. ORR was 15%
`(mm) and 25% (Niv'0+lPl) for evaluable pts; durable responses were
`noted. Updated safety. clinical activity and biomarker analysis will be
`presented. Clinical trial information: NCTl928394.
`
`