Author of

• 20039

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  Poster Display Session (ID 63)

  • Event: ELCC 2017
  • Type: Poster Display Session
  • Track:
  • Presentations: 2
  • Moderators:
  • Coordinates: 5/07/2017, 12:30 - 13:00, Hall 1

  • 19861

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    105P - Prognostic factors in crizotinib (CRZ)-resistant anaplastic lymphoma kinase (ALK+) non-small cell lung cancer (NSCLC) patients (Pts) (ID 469)

    12:30 - 12:30  |  Author(s): W. Reichmann
    • Abstract

    Background:
    The aim of this analysis was to assess prognostic factors in patients with CRZ-resistant ALK+ NSCLC associated with progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) based on the Phase 2 ALTA Trial (NCT02094573) of brigatinib.
    
    Methods:
    Analyses used data from ALTA Arm B (180 mg qd with a 7-day lead-in at 90 mg, N = 110). Potential prognostic factors were evaluated using univariate and multivariate Cox proportional hazards models for PFS and OS, and logistic regression for ORR. Potential prognostic factors included age, sex, race, ECOG performance status, prior radiotherapy (RT), prior RT to brain, prior chemotherapy, prior platinum-based chemotherapy, smoking status, number of prior regimens, best response to prior CRIZ, number of metastatic sites, and active brain lesions. ALTA trial was not powered to detect differences in outcomes by these factors, thus a threshold of p < 0.5 was used to select variables into all models. Factors with hazard ratios >1.30 or < 0.77 were also included in the final models for PFS and OS.
    
    Results:
    As of February 29, 2016, median follow-up was 8.3 months, and independent review committee (IRC) assessed median PFS was 15.6 months [95% CI: 11.0, NR] (31 events). Median OS was not reached (17 deaths). IRC-assessed ORR was 52.7% [95% CI: 43.0%, 62.3%]. Prognostic factors are shown in the table.rnTable: 105PImportant prognostic factors in CRIZ-resistant ALK+ NSCLC treated with brigatinib 180 mg qd with a 7-day lead-in at 90 mg (N = 110)rn

    rnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrn

    Prognostic Factor	PFS (HR [95% CI])*	OS (HR [95% CI])*	ORR (OR [95% CI])**
    Age (per 1-year increase)	–	–	0.98 [0.95, 1.01]
    Sex Male vs female	1.79 [0.84, 3.79]	–	–
    Race Asian vs non-Asian	1.29 [0.55, 3.04]	0.15 [0.02, 1.25]	1.87 [0.73, 5.00]
    ECOG performance status 1 vs 0 2 vs 0	0.72 [0.33, 1.58] 3.24 [0.99, 10.60]	2.56 [0.72, 9.06] 4.02 [0.73, 22.14]	0.64 [0.26, 1.53] 0.19 [0.02, 1.07]
    Prior chemotherapy Yes vs no	0.42 [0.19, 0.95]	0.34 [0.11, 1.04]	1.90 [0.71, 5.24]
    Best response to prior CRIZ CR/PR vs any other status or unknown	0.56 [0.25, 1.27]	0.74 [0.24, 2.33]	1.88 [0.77, 4.70]
    Prior radiotherapy to brain Yes vs no	2.21 [1.02, 4.78]	0.51 [0.17, 1.57]	–
    Active brain lesions Yes vs no	–	0.45 [0.15, 1.39]	–
    Smoking status Never vs current/former/unknown	–	0.49 [0.14, 1.67]	2.45 [1.04, 5.97]
    Number of metastatic sites 3 vs 1-2 4+ vs 1-2	–	1.05 [0.20, 5.58] 2.66 [0.59, 12.03]	0.34 [0.10, 1.08] 0.81 [0.27, 2.36]

    rnAbbreviations: PFS = progression-free survival; OS = overall survival; ORR = objective response rate; HR = hazard ratio; OR = odds ratio; CI = confidence interval; CR = complete response; PR = partial response; ECOG = Eastern Cooperative Oncology Group;rn*HR < 1 indicates lower risk of progression or death vs reference group;rn**OR > 1 indicates higher odds of response vs reference grouprn
    
    Conclusions:
    In this analysis of CRZ-resistant ALK+ NSCLC patients, a history of prior chemotherapy was associated with longer PFS, while prior radiotherapy was associated with shorter PFS, both likely due to unmeasured patient characteristics. Never smokers had more than double the odds of response, versus current or former smokers. ECOG status 2 was nominally associated with shorter PFS and OS and lower ORR, and presence of active brain lesions was associated with longer OS.
    
    Clinical trial identification:
    The trial protocol number is NCT02094573.
    
    Legal entity responsible for the study:
    Evidera Inc.
    
    Funding:
    ARIAD Pharmaceuticals
    
    Disclosure:
    K.L. Reckamp: Consulting or advisory role (ARIAD), research funding (ARIAD). J. Lee, M. Krotneva: Employee of Evidera Inc., which provides consulting services to pharmaceutical organizations. Evidera Inc. received funding from ARIAD pharmaceuticals. J. Huang: Employment, consulting or advisory role (ARIAD). W. Reichmann, D. Kerstein, H. Huang: Employment, stock shareholder (ARIAD). All other authors have declared no conflicts of interest.
    
    

  • 19853

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    97P - Brigatinib in crizotinib-refractory ALK+ NSCLC: Updates from the pivotal randomized phase 2 Trial (ALTA) (ID 247)

    12:30 - 12:30  |  Author(s): W. Reichmann
    • Abstract

    Background:
    In a phase 1/2 trial (NCT01449461), the investigational next-generation anaplastic lymphoma kinase (ALK) inhibitor brigatinib (BRG) showed promising activity in crizotinib-treated ALK-positive non–small cell lung cancer (ALK+ NSCLC) patients (pts); because tumor responses and adverse events (AEs) varied with starting dose, two BRG regimens were evaluated in ALTA (NCT02094573).
    
    Methods:
    Pts with crizotinib-refractory advanced ALK+ NSCLC were stratified by presence of brain metastases and best response to prior crizotinib and randomized 1:1 to receive BRG at 90 mg qd in arm A or 180 mg qd with a 7-day lead-in at 90 mg in arm B. Investigator-assessed confirmed objective response rate (ORR) per RECIST v1.1 was the primary endpoint.
    
    Results:
    222 pts were enrolled (112 in arm A, 110 in arm B); median age was 54 years, 57% were female, 74% had received chemotherapy, and 69% had brain metastases. As of 29 February 2016, 57%/69% of pts in arms A/B were receiving BRG, with 7.8/8.3-month median follow-up. Investigator-assessed efficacy by arm and subgroup is shown below. Per independent review committee, as of 16 May 2016, confirmed ORR was 48%/53% and median PFS was 9.2/15.6 months in arms A/B. Treatment-emergent AEs with ≥25% overall frequency (A/B, n = 109/n=110 treated) were nausea 33%/40%, diarrhea 19%/38%, headache 28%/27%, and cough 18%/34%; grade ≥3 events with ≥3% frequency were hypertension 6%/6%, increased blood creatine phosphokinase 3%/9%, pneumonia 3%/5%, and increased lipase 4%/3%. A subset of pulmonary AEs with early onset (median onset: Day 2) occurred in 14/219 (6%) treated pts (3%, grade ≥3); no such events occurred after escalation to 180 mg in arm B, and 7/14 pts were successfully retreated.
    
    Conclusions:
    BRG yielded substantial efficacy, with an acceptable safety profile, in both arms. 180 mg with 90 mg lead-in showed an improvement in efficacy endpoints, particularly PFS, with no increase in early pulmonary AEs, compared with 90 mg. Investigator-Assessed Efficacy by Subgroup.rnTable: 97PDrn

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    rn	Arm A n = 112	Arm B n = 110	Total N = 222
    Confirmed ORR, n/N (%)	rn	rn	rn
    All pts[a]	50/112 (45)	59/110 (54)	109/222 (49)
    Race	rn	rn	rn
    Asian	18/39 (46)	18/30 (60)	36/69 (52)
    Non-Asian	32/73 (44)	41/80 (51)	73/153 (48)
    Prior chemotherapy	rn	rn	rn
    Yes	35/83 (42)	44/81 (54)	79/164 (48)
    No	15/29 (52)	15/29 (52)	30/58 (52)
    Best response to prior crizotinib	rn	rn	rn
    CR or PR	36/71 (51)	47/73 (64)	83/144 (58)
    Other	14/41 (34)	12/37 (32)	26/78 (33)
    Baseline brain metastases	rn	rn	rn
    Yes	31/80 (39)	43/74 (58)	74/154 (48)
    No	19/32 (59)	16/36 (44)	35/68 (51)
    Median PFS, months	rn	rn	rn
    All pts	9.2	12.9	11.1
    Race	rn	rn	rn
    Asian	8.8	11.1	11.1
    Non-Asian	9.2	12.9	11.8
    Prior chemotherapy	rn	rn	rn
    Yes	8.8	12.9	11.8
    No	9.2	8.1	9.2
    Best response to prior crizotinib	rn	rn	rn
    CR or PR	11.1	15.6	15.6
    Other	7.4	12.9	9.2
    Baseline brain metastases	rn	rn	rn
    Yes	9.2	11.8	11.1
    No	7.4	15.6	15.6

    rnCR = complete response, ORR = objective response rate, PFS = progression-free survival, PR = partial responsernaPrimary endpointrn
    
    Clinical trial identification:
    NCT02094573
    
    Legal entity responsible for the study:
    ARIAD Pharmaceuticals, Inc.
    
    Funding:
    ARIAD Pharmaceuticals, Inc.
    
    Disclosure:
    M. Tiseo: Consulting or advisory role (AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, Novartis, Otsuka, Pierre Fabre), research funding (ARIAD). K.L. Reckamp: Consulting or advisory role (ARIAD), research funding (ARIAD). H.L. West: Consulting or advisory role (ARIAD, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Merck, Novartis, Pfizer, Roche/Genentech, Trovagene), speakers’ bureau (ARIAD, Eli Lilly, Roche/Genentech). H.J. Groen: Consulting or advisory role (Eli Lilly, MSD, Novartis, Pfizer, Roche). C.J. Langer: Honoraria (BMS, Lilly/ImClone, Roche/Genentech), consulting or advisory role (Abbott, ARIAD, AstraZeneca, Bayer/Onyx, BMS, Cancer Support Community, Celgene, Clarient, Clovis Oncology, Lilly/ImClone, Merck, Millennium, Roche/Genentech), research funding (Advantagene, ARIAD, Celgene, Clovis Oncology, GSK, Inovio, Merck, Roche/Genentech). W. Reichmann, D. Kerstein: Employment, stock and other ownership interests (ARIAD). D.R. Camidge: Honoraria (ARIAD), research funding (ARIAD). All other authors have declared no conflicts of interest.
    
    

• 19973

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  Targeted therapies and management of brain metastasis (ID 40)

  • Event: ELCC 2017
  • Type: Proffered Paper session
  • Track:
  • Presentations: 1
  • Moderators:D.P. Carbone, S. Ekman
  • Coordinates: 5/06/2017, 16:45 - 18:15, Room A

  • 19978

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    87O - Brigatinib in ALK+ NSCLC pts with intracranial CNS metastases in 2 clinical trials (ID 241)

    17:36 - 17:48  |  Author(s): W. Reichmann
    • Abstract
    • Presentation
    • Slides

    Background:
    The investigational next-generation anaplastic lymphoma kinase (ALK) inhibitor brigatinib is being evaluated in patients (pts) with ALK-positive non–small cell lung cancer (ALK+ NSCLC) in a phase 1/2 trial (Ph1/2) and a pivotal phase 2 trial (ALTA); most of these pts had intracranial central nervous system (CNS) metastases at baseline.
    
    Methods:
    In Ph1/2 (NCT01449461), pts with advanced malignancies, including ALK+ NSCLC, received brigatinib (30–300 mg/d). In ALTA (NCT02094573), crizotinib-resistant pts with advanced ALK+ NSCLC received brigatinib at 90 mg qd in arm A or 180 mg qd with a 7-day lead-in at 90 mg in arm B. ALK+ NSCLC pts with baseline brain metastases were analyzed. CNS efficacy in both trials and safety in ALTA are shown.
    
    Results:
    In Ph1/2 and ALTA, 50/79 (63%) and 154/222 (69%) ALK+ NSCLC pts had baseline brain metastases based on independent review committee (IRC) and investigator assessment, respectively. Most pts had received chemotherapy (Table). In Ph1/2, 25/50 (50%) pts were receiving brigatinib as of 16 November 2015; in ALTA, 101/154 (66%) pts were receiving brigatinib as of 29 February 2016. In pts with measurable brain lesions, confirmed intracranial objective response rate was 53% in Ph1/2 and 42%/67% in ALTA A/B (Table). In pts with only nonmeasurable brain lesions, 35% (11/31) in Ph1/2 and 7% (4/54)/18% (10/55) in ALTA A/B had confirmed complete resolution of brain lesions. Further data are shown in the table. The most common treatment-emergent adverse events (TEAEs) in the 151 treated ALTA pts with baseline brain metastases were nausea (A/B, 32%/43%), headache (30%/30%), diarrhea (18%/36%), cough (21%/30%), and vomiting (25%/26%); the most common grade ≥3 TEAEs were increased blood creatine phosphokinase (1%/11%), hypertension (4%/7%), increased lipase (3%/3%), and pneumonia (1%/4%).
    
    Conclusions:
    Brigatinib yielded substantial clinical activity in ALK+ NSCLC pts with brain metastases in 2 trials.rnTable: 87OBaseline characteristics and IRC-assessed intracranial efficacy of brigatinib in ALK+ NSCLC Pts with brain metastases at baselinern

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    rn	Ph1/2 n = 50	ALTA Arm A n = 80	ALTA Arm B n = 74
    Median age, years	53	49	55
    Received prior chemotherapy, %	76	74	76
    Crizotinib-naive, %	8	0	0
    Pts evaluable for intracranial efficacy by IRC, n[a]	46	80	73
    Median iPFS, months	14.6	15.6	12.8
    Pts with measurable brain lesions, n	15	26	18
    iORR, n (%)	8 (53)	11 (42)	12 (67)
    iDCR, n (%)	13 (87)	22 (85)	15 (83)
    No rad/active[b] subset, n	9	19	15
    iORR, n (%)	6 (67)	8 (42)	11 (73)
    iDCR, n (%)	8 (89)	16 (84)	14 (93)

    rniDCR = intracranial disease control rate, iORR = intracranial objective response rate (confirmed), iPFS = intracranial progression-free survivalrnaLast scan date: 8 October 2015 in Ph1/2; 14 April 2016 in ALTArnbNo prior brain radiotherapy in Ph1/2; active (untreated or treated and progressed) brain lesions in ALTArn
    
    Clinical trial identification:
    NCT01449461 and NCT02094573
    
    Legal entity responsible for the study:
    ARIAD Pharmaceuticals, Inc.
    
    Funding:
    ARIAD Pharmaceuticals, Inc.
    
    Disclosure:
    M. Tiseo: Consulting or advisory role (AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, Novartis, Otsuka, Pierre Fabre), research funding (ARIAD). R.M. Huber: Honoraria (ARIAD, AstraZeneca, BMS, Boehringer Ingelheim, Pfizer, Roche), consulting or advisory role (BMS, Boehringer Ingelheim, Celgene, Clovis Oncology, Eli Lilly, Novartis, Roche), research funding (Pierre Fabre). L.A. Bazhenova: Stock and other ownership interests (Epic Sciences), honoraria (Novartis), consulting or advisory role (AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Clovis Oncology, Genoptix, Heat Biologics, Pfizer, Roche/Genentech, Seattle Genetics, Trovagene), speakers bureau (AstraZeneca, Novartis, Pfizer, Roche/Genentech), research funding (AbbVie, ARIAD, Astellas, Astex, AstraZeneca/MedImmune, Boehringer Ingelheim, Chugai, Clovis Oncology, Eisai, Eli Lilly, Heat Biologics, Johnson & Johnson, Merck, Mirati, NanoCarrier, Novartis, Pfizer, Roche/Genentech). S-H.I. Ou: Advisory board (ARIAD). W. Reichmann, J. Haney, D. Kerstein: Employment, stock and other ownership interests (ARIAD). D.R. Camidge: Honoraria (ARIAD), research funding (ARIAD). S.N. Gettinger: Consulting or advisory role (ARIAD, BMS, Janssen), research funding (ARIAD, AstraZeneca/MedImmune, BMS, Boehringer Ingelheim, Incyte, Pfizer, Roche/Genentech). All other authors have declared no conflicts of interest.
    
    

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