tbuckley/cabot-search huggingface dataset:
Clinical trials of MPDL3280A (anti-PDL1) in patients (pts) with non-small cell lung cancer (NSCLC).
Authors: Naiyer A. Rizvi, Laura Quan Man Chow, Luc Yves Dirix, Scott N. Gettinger, Michael S. Gordon, Fairooz F. Kabbinavar, Joachim Von Pawel, Jean-Charles Soria, Colombe Chappey, Ahmad Mokatrin, Alan Sandler, Daniel Waterkamp, David R. Spigel
Journal: Journal of Clinical Oncology (2014)

TPS8123 Background: Blocking the PD-L1/PD-1 immune inhibitory signals can reinvigorate preexisting anticancer immunity and can lead to durable responses in NSCLC. MPDL3280A is a human anti-PD-L1 monoclonal antibody that contains an engineered Fc-domain. MPDL3280A targets PD-L1, preventing binding to its receptors PD-1 and B7.1, thus restoring tumor-specific T-cell immunity. MPDL3280A does not disrupt the PD-L2/PD-1 interaction, which is potentially implicated in autoimmune lung toxicity. In a Phase I study, MPDL3280A led to antitumor responses, with an overall response rate (ORR) of 23% (12/53) in previously-treated NSCLC pts, 46% (6/13) in those pts with a PD-L1 IHC score of 2 or 3 and 83% (5/6) in those pts with a PD-L1 IHC score of 3. Based on these results, we initiated a clinical program examining unselected and PD-L1-positive pts with locally advanced or metastatic NSCLC. Here, we describe the BIRCH and OAK trials. Methods: Both studies require pts aged ≥ 18 y with an ECOG status of 0 or 1 and measurable disease (RECIST v1.1). Pts receive MPDL3280A (1200 mg IV) q3w for up to 16 cycles (or 12 months) in the absence of overt toxicity or deteriorative progressive disease. Pts with autoimmune disease, active CNS metastases and/or prior immune checkpoint blockade are excluded. For BIRCH, a Phase II, single-arm study, ≈ 300 pts (3 cohorts; chemo-naive, single prior platinum-based regimen and ≥ 2 prior therapies) with PD-L1-positive tumors receive MPDL3280A. Chemo-naive pts with a sensitizing EGFR mutation or an ALK rearrangement are excluded. The primary end-point is ORR (RECIST v1.1). Recruitment is ongoing (NCT02031458). OAK is a global Phase III, multicenter, randomized, open-label, efficacy and safety evaluation of MPDL3280A compared with docetaxel after failure of a platinum-containing chemotherapy. Pts (≈ 850) receive docetaxel (75 mg/m2 IV) or MPDL3280A. Eligible pts are enrolled regardless of PD-L1 status but stratified by PD-L1 expression levels. The primary objective is a comparison of OS. Secondary objectives include ORR, PFS and other efficacy criteria. Recruitment begins Q1 of 2014 (NCT02008227). Clinical trial information: NCT02031458, NCT02008227.
Efficacy and CNS progression analysis from the randomized phase 2 trial of neratinib + paclitaxel vs trastuzumab + paclitaxel as first-line treatment for HER2+ metastatic breast cancer (NEfERTT).
Authors: Ahmad Awada, Ramon Colomer, Igor Bondarenko, Kenichi Inoue, Rajendra A. Badwe, Georgia Demetriou, Xiaojia Wang, Vitaly Smirnov, Soo-Chin Lee, Ajay O. Mehta, Sung-Bae Kim, Zhen-Zhou Shen, Thomas Denis Bachelot, Chanchal Goswami, S. V. S. Deo, Ron Bose, Alvin Wong, Feng Xu, Richard Bryce, Lisa A. Carey
Journal: Journal of Clinical Oncology (2015)

610 Background: This large randomized open-label phase 2 trial compared the efficacy and safety of Neratinib (N), the irreversible pan-HER tyrosine kinase inhibitor, + Paclitaxel (P) vs Trastuzumab (T) + P as first-line treatment in HER2+ metastatic breast cancer (MBC). Methods: 479 pts were enrolled between 08/2009 and 08/2011. Women ≥18y with locally recurrent or MBC, HER2 gene amplification/HER2 overexpression, no progression within 12m (neo)adjuvant therapy, and no prior treatment for advanced disease were eligible. Pts were randomized to oral N (240mg od) + P or T+P. Dosing: T 4mg/kg iv then 2mg/kg iv weekly, P 80mg/m2 iv weekly 3/4w. Primary endpoint: progression-free survival (PFS). Secondary endpoints: overall survival (OS); overall response rate (ORR); duration of response; clinical benefit rate; CNS progression; safety. PFS analysis was ITT by stratified log-rank test. Randomization was stratified by region, prior T, prior lapatinib, ER/PR status. 304 PFS events were required to detect 30% improvement in median PFS with 80% power (2-sided α=0.15). Results: 479 pts made up the ITT population (6 pts in NP arm and 12 pts in TP arm had known brain metastases at baseline; other baseline characteristics were balanced). Main efficacy findings are shown below. Most common adverse events (AEs) with NP vs TP were: diarrhea 93 vs 33% (G3 30 vs 4%; no G4; G3 median duration of 4.5d); nausea 44 vs 30% (G≥3 2 vs 1%); vomiting 36 vs 16% (G≥3 3 vs 1%); fatigue 32 vs 27% (G≥3 3 vs 3%); rash 31 vs 24% (G≥3 1 vs < 1%); cardiac disorders 2.5 vs 5.1% (G≥3 < 1 vs < 1%). Conclusions: NP has similar efficacy to TP; of interest, NP may be more effective than TP in reducing CNS progression. With no primary loperamide prophylaxis, diarrhea was significantly higher with NP than TP; non-GI AEs occurred at similar rates in both arms. Clinical trial information: NCT00915018. Efficacy endpoint N + P (n=242) T + P (n=237) Hazard ratio (95% CI) P-value Median PFS, months (95% CI) 12.9 (11.0–14.8) 12.9 (11.1–14.7) 1.03 (0.83–1.29) 0.777 ORR, n (%) 181 (75) 183 (77) – 0.595 CNS progressiona, n (%) 19 (8) 38 (16) – 0.0037 KM cumulative incidence of CNS recurrence, % 14.4 32.1 0.46 (0.26–0.81) 0.006 a49 events were CNS only.
Long-term functional results and quality of life after open partial laryngectomy and non-surgical larynx preservation.
Authors: Beatriz Castelo, Alejandro Castro, Luis Alberto Glaria, Alvaro Pinto, Antonio del Palacio, Andrés Redondo, Ricardo Bernaldez, Ana Escribano, Javier Gavilan, Enrique Espinosa
Journal: Journal of Clinical Oncology (2015)

e17056 Background: Classic open partial laryngectomy (OPL) techniques allow the preservation of laryngeal functions with excellent local control rates. Different combinations of radiotherapy and chemotherapy have been established to preserve the larynx. The key to success is the proper selection of patients (pts) to achieve the best long-term quality of life (QOL) without compromising survival. Methods: A retrospective review of pts with squamous cell laryngeal or hypopharyngeal carcinoma treated at our institution between 1999 and 2009 was performed. Pts primary treated with either OPL or any non-surgical (N-S) protocol were considered. T1 tumors were excluded as most of them were treated with transoral laser surgery. A functional larynx (FL) was considered when the patient was free of tracheostomy and feeding tube at the time of last contact. Actuarial rates for FL and for free of disease with FL were calculated using the Kaplan-Meier method. A quality of life survey was performed with those pts that were alive, free of disease, and with a FL. Results: Eighty-five pts were identified: 52% had been treated with OPL and 48% with chemo-radiotherapy. Minimum and median follow-up were 20 and 50 months (m). A FL was preserved in 75% of surgical pts and 63% of N-S pts. The number of FL remains stable in the surgical group 27 m after treatment, although it continues decreasing over time in the N-S group. 44 pts were alive, free of disease and with FL at the time of the survey, and 33 (75%) answered the questionnaire. Mean time since treatment to the QOL survey was 83 m. Median scores of the three questionnaires were very high for the whole population. Pts in the N-S group scored significantly worse regarding pain, teeth problems, and sticky saliva. No other statistically significant difference was found in QOL scores between surgical and N-S groups. Conclusions: . The chance to preserve a long-term FL is higher with OPL than with N-S protocols. These techniques are considered the most appropriate treatment for moderately advanced laryngeal and hypopharyngeal cancer. N-S treatment is offered to pts whose only surgical option is total L. If a FL is preserved, quality of life with either treatment is comparable.
Effect of BPM 31510 on survival outcomes when used in combination with gemcitabine in a preclinical model of pancreatic cancer.
Authors: Joaquin J. Jimenez, Lucia M Mauro, Viacheslav R Akmaev, John McCook, Min Du, Shen Luan, Paul Y. Song, Rangaprasad Sarangarajan, Niven R Narain
Journal: Journal of Clinical Oncology (2012)

e14593 Background: BPM 31510 is a novel small molecule that targets the metabolic machinery of the cancer microenvironment to create a hallmark shift from lactate dependency towards mitochondrial oxidative phosphorylation, reversing the Warburg effect. Effector downstream signaling results in re-capitulation of BCL-2 mediated apoptosis and disruption in tumor vasculature by modulation of VEGF. This study reports on the therapeutic benefit associated with BPM 31510 used in combination with gemcitabine in animal model of pancreatic cancer. Methods: The NGS mouse devoid of innate and adaptive immune system were implanted with human pancreatic cancer cells, Mia PaCa-2. The animals were randomized (n=30/group) to the following dose regiment cohorts: 50 mg/kg body weight (BW) once or twice daily ± gemcitabine (150 mg/kg BW once/week) for 3 weeks followed by one week rest. A group of animals received 75 mg/kg BW thrice daily ± gemcitabine (150 mg/kg BW once/week) for 3 weeks followed by one week rest. Untreated or group treated with gemcitabine alone with corresponding treatment regimen served as controls. The primary objective was to evaluate the difference in overall survival of the animals when treated with gemcitabine alone compared to combination regimens with BPM 31510. Results: All tumor bearing untreated animals (control arm) expired by Day 21 of the study. In contrast, the once daily BPM 31510 dose regimen was associated with significant increase in duration of overall survival (p&lt;0.009) with all animals expiring by Day 142 compared to gemcitabine alone. The combination of BPM 31510 with gemcitabine was associated with significantly increase in overall survival compared to BPM 31510 (p=0.002) or gemcitabine (p = 7.3E-8) alone. This was associated with significant reduction in tumor size and weight (p&lt;0.001). Increased frequency of BPM 31510 dosing alone or in combination with gemcitabine was associated with significant increases in survival rates. Conclusions: The data herein suggest that BPM 31510 may be a viable agent for combination therapy in pancreatic cancer via employment of a novel metabolic pathways.
A phase Ib study of combined angiogenesis blockade with REGN910 (SAR307746), a selective monoclonal antibody (MAb) against angiopoietin-2 (Ang2) and ziv-aflibercept in patients with advanced solid tumor malignancies.
Authors: Lieve Adriaens, Kyriakos P. Papadopoulos, Donna M. Graham, Amita Patnaik, Albiruni R.A. Razak, Anthony W. Tolcher, Lillian L. Siu, Drew Warren Rasco, Pamela Trail, Carrie M. Brownstein, Israel Lowy
Journal: Journal of Clinical Oncology (2013)

TPS2618 Background: REGN910 is a selective, fully human Angiopoietin-2 (ANG-2) MAb, which potently blocks signaling through the Tie2 receptor. Ziv-aflibercept (ZAFL) is a recombinant human fusion protein that acts as a decoy receptor for vascular endothelial growth factor (VEGF)-A, VEGF-B, and placental growth factor (PlGF), thereby preventing the interaction of these ligands with their receptors. In several mouse xenograft models, combination of the 2 anti-angiogenic compounds, REGN910 and ZAFL, demonstrated significantly enhanced tumor growth inhibition relative to either agent alone, suggesting that dual angiogenic blockade is worth exploring in cancer patients. Methods: This phase 1b study employs a standard 3+3 dose escalation design exploring 5 different combination treatment dose levels of REGN910 and ZAFL. Once the recommended phase 2 dose (RD) of the combination treatment is determined, additional patients will be enrolled in a safety expansion cohort, for a planned total enrollment of up to 40 patients. The primary study objectives are to evaluate the safety and determine the RD of the 2 drugs in combination when both are administered IV every 2 weeks in patients with advanced solid tumors. Secondary endpoints include characterization of the PK and potential immunogenicity of REGN910 and ZAFL when given in combination, evaluation of correlative PD biomarkers related to REGN910 and ZAFL, and identification of antitumor activity. Enrollment to cohorts 1 and 2 has been completed without DLT. Enrollment to cohort 3 opened in December 2012. Updated enrollment status will be presented. Reference: ClinicalTrials.gov Identifier: NCT01688960. Clinical trial information: NCT01688960.
A Versatile DNA/RNA NGS Targeted Capture Strategy for Detection of Fusion Genes in Pediatric ALL
Authors: Grazia Fazio, Andrea Grioni, Tomas Reigl, Silvia Rigamonti, Vojtech Bystry, Simona Songia, Andrea Biondi, Nikos Darzentas, Giovanni Cazzaniga
Journal: Blood (2016)
Phase 1 study of ZW25, a bispecific anti-HER2 antibody, in patients with advanced HER2-expressing cancers.
Authors: Diana Felice Hausman, Erika Paige Hamilton, Muralidhar Beeram, Jamuna Thimmarayappa, Gordon Ng, Funda Meric-Bernstam
Journal: Journal of Clinical Oncology (2017)

TPS215 Background: HER2 is expressed above normal levels by many cancers, including a range of gastrointestinal tumors. While HER2 can contribute to tumor growth and survival even when expressed at low levels, antibody-based HER2 targeted therapy has shown efficacy only in breast (trastuzumab [T], pertuzumab [P]) or gastric cancers (T) with the highest levels of HER2 expression or gene amplification. Therefore, there remains significant medical need, particularly for cancers with lower HER2 levels or more heterogeneous patterns of expression. ZW25 is a novel humanized bispecific antibody directed against two distinct epitopes of HER2. The unique structure of ZW25 leads to greater cell decoration and receptor internalization than T, even in the setting of low levels of HER2 expression. In preclinical models, ZW25 has demonstrated greater activity than T in both HER2 high and HER2 low-expressing cancers, including gastric cancer. This first-in-human study will evaluate the safety and preliminary anti-tumor activity of ZW25 in patients with advanced HER2-expressing cancers. Methods: This is a 2-part Phase 1 study utilizing 3+3 dose escalation (Part 1) and expansion cohorts (Part 2) to evaluate the MTD, safety, PK, and anti-tumor activity of ZW25 IV once per week in patients with locally advanced, unresectable and/or metastatic HER2-expressing cancers. Eligibility requirements include any HER2 1+, 2+, or 3+ cancer (Part1) or 2+/FISH negative breast or gastric cancer (Part 2) that has progressed after all approved therapies; ECOG PS ≤ 1; normal left ventricular function; and measurable disease per RECIST 1.1 (Part 2). Assessments include collection of adverse events and laboratory abnormalities, tumor response per RECIST 1.1 and exploratory response biomarkers as well as PET. Recruitment is ongoing at 3 centers in the United States. Clinical trial information: NCT02892123.
Study of the medical treatment of extrahepatic bile duct cancer at Misawa City Hospital.
Authors: Kazuhiro Suzuki, Ryosuke Tsuya, Rie Ota, Kiyoto Tsushima, Soh Saitoh, Yuh Sakata
Journal: Journal of Clinical Oncology (2014)

e15112 Background: A biliary tract cancer is a disease with a bad prognosis and a high mortality rate. Although Gemcitabine, Fluopyrimidime Aniticancer Drugs, and drugs containing platinum are used as chemotherapy, radical surgery is the only method of enabling recovery. This time we studied the medical treatment of Stage I to IV of the extrahepatic bile duct cancer at our hospital. Methods: We studied the effect of various medical treatments on 40 patients of stage I to IV of the extrahepatic bile duct cancer with no medical historical verification of chemotherapy. These patients matched grade 0 to 4 accoding to the Eastern Cooperative Oncology Group with a performance status chart. The decreasing value of bilirubin, the length of the first hospitalization, and the over all survival were retroacted and examined. Results: From April, 2005 to January, 2013, 40 cases were analyzed. (a)The group of
A phase I study of the AKT inhibitor MK-2206 plus hormonal therapy in postmenopausal women with estrogen receptor positive (ER+) metastatic breast cancer (MBC).
Authors: Cynthia X. Ma, Feng Gao, Michael Naughton, Timothy J. Pluard, Steven Sorscher, Allison N Creekmore, Zhanfang Guo, Farrokh Dehdashti, Ben Ho Park, Albert C. Lockhart, L. Austin Doyle, Matthew J. Ellis, Bracha Erlanger
Journal: Journal of Clinical Oncology (2014)

553 Background: Inhibition of the PI3K/AKT pathway synergize with hormonal therapy for ER+ BC in preclinical studies. We conducted a phase I trial of MK-2206 plus anastrozole (A) (Phase IA and IB) or fulvestrant (F) (Arm C) or A+F (Arm D) in postmenopausal women with ER+ MBC to obtain the recommended phase II treatment dose (RPTD). Methods: phase IA employed a 3+3 design to determine the maximum tolerated dose (MTD) of MK-2206. Pts treated at the MTD were eligible for Phase IB to determine RPTD based on first 3-cycle adverse events (AE). Arms C and D evaluated whether MK-2206 at the RPTD was tolerable when combined with F or A+F. Cycle 1 day 1 (C1D1) MK-2206 began after at least 2 weeks (wks) of A and/or 4 wks of F. FDG PET was performed in Phase IA on C1D1 prior to MK-2206 and C1D2. Tumor was measured every 3 28-day cycles. Baseline blood was assayed for PIK3CA E545K and H1047R mutations. Results: Thirty one pts, median age 55 (range 32-79) years, were enrolled (Table 1). MK-2206 was administered PO wkly, with A and/or F. Because grade (G)3 rash occurred in 3 of the first 8 pts, prophylactic prednisone was added subsequently. Treatment was well tolerated. G3 rash was the only dose limiting toxicity (DLT). The most common all-cycle AEs were rash (n=10), hyperglycemia (n=11), and hypophosphatemia (n=5). The MTD and RPTD of MK-2206, plus A and/or F, were 150mg PO wkly with prophylactic prednisone. Median SUV reduction was 14.5% (-58% to 19%) on C1D2 compared to C1D1. Twenty six pts, with a median of 1 (0-7) metastatic therapy, were evaluable for response. Eleven pts, 42% (95% CI 23% - 63%), derived clinical benefit, including 2 PR and 9 SD >= 6 months. Time to progression was significantly associated with prior adjuvant hormonal therapy (p=0.02), but not with circulating PIK3CA mutation or hyperglycemia. Tumor specimen analysis is ongoing. Conclusions: MK-2206 plus hormonal therapy was well tolerated with anti-tumor activity observed. Rash was common but incidence reduced with prophylactic prednisone. Clinical trial information: NCT01344031. Arm Dose Level MK-2206 (mg) N N (DLT) 1A 1* 150 5 2 1A -1 100 3 1 1A/1B 1# 150 6 0 1A 2# 200 2 2 Arm C 1# 150 8 1 Arm D 1# 150 7 1 * Starting dose #prednisone 20mg PO the day before, the day of, and the day after MK-2206.
Retrospective analysis of type of KRAS mutation (mut) and response to first-line platinum-based chemotherapy (PC) in non-small cell lung cancer (NSCLC) patients (pts).
Authors: Wouter Willem Mellema, Lucie Masen-Poos, Lizza Hendriks, Anthonie Van Der Wekken, Joachim Aerts, Judith Herder, Jos Stigt, Ben Van Den Borne, Michel M van den Heuvel, Ellen Pouw, Anne-Marie C. Dingemans, Egbert F. Smit
Journal: Journal of Clinical Oncology (2014)

8061 Background: Improving clinical outcome of pts with advanced NSCLC with a KRAS mut is challenging. Previous research indicated that different types of KRAS mut respond differently to chemotherapy regimens. This may impact treatment strategy in this group of pts. Methods: Consecutive pts with advanced NSCLC and known KRAS mut status, treated with first-line PC were retrieved from different hospital databases. Primary objective: Differences in overall response rate (ORR), progression free survival (PFS) and overall survival (OS) between different types of PC per type of KRAS mut. Χ2-test and log rank test were used and pts were stratified by KRAS amino acid substitution (sub). Results: 305 pts (92% stage IV) from 10 hospitals, treated between 2008 and 2013, were included. Most common mut were G12C (47%), G12V (20%) and G12D (10%); 90% of pts had a codon 12 mut. Pts were treated with cisplatin (n=155) or carboplatin (n=150), combined with pemetrexed (PEM; n=194), gemcitabine (GEM; n=50), taxanes (TAX; n=27) or paclitaxel plus bevacizumab (CPB; n=34). Treatment with CPB resulted in significant better ORR compared to other regimen (61% vs. 33% (TAX), 29% (GEM), 22% (PEM); p<0.001). The median OS for pts with codon 13 mut (n=20) was 6.4 months and for codon 12 mut (n= 262) 9.8 months (p=0.38). Pts with codon 12 mut were clustered into groups according to sub. Results are summarized in Table. Conclusions: CPB had best ORR in KRAS mut pts. G>A sub pts showed a trend to poor OS. PC treatment was comparable per type of KRAS mut. These observations encourages study in a larger group of patients. KRAS sub codon 12 (n) ORR Median PFS in months (95% CI) Median OS in months (95% CI) G>A (34) PEM (21) GEM (4) TAX (4) CPB (5) 10% 25% 50% 40% p=.18 4.1 (3.6-4.5) 4.0 (0-10.7) 3.2 (1.3-5.0) 2.5 (2.4-2.7) 8.5 (5.7-11.2) 5.6 (0-13.3) 3.6 (0.8-6.3) 4.2 (0-16.4) G>T (203) PEM (123) GEM (41) TAX (17) CPB (22) 22% 29% 29% 64% p<.01 5.0 (3.7-6.2) 3.9 (1.7-6.1) 4.9 (3.5-6.3) 5.6 (2.7-8.5) 8.3 (7.3-9.4) 9.3 (1.2-17.3) 10.5 (0-22.8) 14.3 (9.8-18.7) G>C (24) PEM (18) GEM(1) TAX(1) CPB(4) 33% 0% 0% 100% p=.04 7.6 (3.3-11.9) 14.3 (-) 10.9 (-) - p=.47 16.6 (10.5-22.6) 21.7 (-) 24.8 (-) - p=.63
EML4-ALK rearrangement in blood platelets and outcome to crizotinib in non-small-cell lung cancer patients.
Authors: Niki Karachaliou, R. Jonas A. Nilsson, Jordi Berenguer, Ana Gimenez Capitan, Pepijn Schellen, Cristina Teixido, Justine Leonie Kuiper, Esther Drees, Magda Grabowska, Marte van Keulen, Jihane M. Tannous, Danielle Heideman, Erik Thunnissen, Anne-Marie C. Dingemans, Santiago Viteri Ramirez, Bakhos A. Tannous, Ana Drozdowskyj, Egbert F. Smit, Thomas Wurdinger, Rafael Rosell
Journal: Journal of Clinical Oncology (2015)

8082 Background: Non-small-cell lung cancer (NSCLC) with EML4-ALK rearrangements is sensitive to crizotinib. However, despite initial response most patients (p) will eventually relapse and monitoring EML4-ALK rearrangements over the course of treatment may help identify them. Challenges associated with serial tumor biopsies have highlighted the need for blood-based assays for monitoring biomarkers. Platelets can sequester RNA released by tumor cells and are an attractive source for non-invasive biomarker assessment. Methods: EML4-ALK rearrangements were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) in platelets and plasma isolated from blood obtained from 77 NSCLC p, 38 of whom had EML4-ALK-rearranged tumors. In a subset of 29 p with EML4-ALK-rearranged tumors treated with crizotinib, EML4-ALK rearrangements in platelets were correlated with progression-free survival (PFS) and overall survival (OS). Results: The study was designed with three parallel objectives: firstly to determine the sensitivity and specificity of detecting EML4-ALK rearrangements in platelets with plasma serving as a control biosource; secondly, to examine the potential impact of EML4-ALK rearrangement in platelets on outcome to crizotinib; thirdly, to test the feasibility of monitoring a p throughout treatment with EML4-ALK rearrangement assessment in platelets. RT-PCR demonstrated 65% sensitivity and 100% specificity for detection of EML4-ALK rearrangements in platelets. In the subset of 29 p treated with crizotinib, PFS was 3.7 months for p with EML4-ALK+ platelets and 16 months for those with EML4-ALK− platelets (hazard ratio, 3.5; P = 0.02). Monitoring EML4-ALK rearrangements in platelets of one index p over a period of 30 months revealed crizotinib resistance two months prior to radiographic disease progression. Conclusions: Platelets may provide a useful source for non-invasive assessment of EML4-ALK rearrangements and may prove useful for predicting outcome to crizotinib. Serial analyses of EML4-ALK rearrangements in platelets may help improve clinical decisions based on radiographic imaging alone by detecting resistance to therapy sooner.