- N. Leighl (Toronto, Canada)
- T. Mok (Shatin, Hong Kong PRC)
84O - Phase I study of gefitinib (G) + durvalumab (D) for locally advanced/metastatic non-small cell lung cancer (NSCLC) harbouring epidermal growth factor receptor (EGFR) sensitising mutations
- D. Gibbons (Houston, TX, United States of America)
- B. Creelan (Tampa, FL, United States of America)
- T. Yeh (Boston, MA, United States of America)
- S. Kim (Seoul, Korea, Republic of)
- N. Nogami (Matsuyama City, Japan)
- D. Kim (Seoul, Korea, Republic of)
- L. Chow (Seattle, WA, United States of America)
- S. Kanda (Tokyo, Japan)
- R. Taylor (Cambridge, United Kingdom)
- W. Tang (Gaithersburg, MD, United States of America)
- M. Tang (Gaithersburg, MD, United States of America)
- H. Angell (Cambridge, United Kingdom)
- M. Roudier (Cambridge, United Kingdom)
- M. Marotti (Cambridge, United Kingdom)
- D. Gibbons (Houston, TX, United States of America)
Abstract
Background
G and D have both shown efficacy in patients (pts) with NSCLC; G + D may improve durability of response.
Methods
This Phase 1 dose escalation (Part A) and expansion (Part B) study (NCT0208811) assessed G 250 mg once daily + D 3 mg/kg (Part A) or 10 mg/kg (Parts A + B) every 2 weeks in pts with locally advanced/metastatic NSCLC. Part A pts were all comers who had failed to respond/relapsed following standard treatment (Tx). Part B pts had sensitising EGFR mutations and were tyrosine kinase inhibitor naïve: Arms 1 + 1a received G + D; Arm 2 received G (4 weeks) before G + D. Primary objective: safety/tolerability. Secondary objectives: pharmacokinetics (PK), pharmacodynamics, immunogenicity (anti-drug antibodies [ADAs]) and efficacy. Exploratory objective: evaluation of biomarkers (e.g. tumour programmed cell death ligand-1 [PD-L1]) and relationship with efficacy.
Results
There were no dose limiting toxicities in Part A (n = 16) and D 10 mg/kg was used in Part B. In Part B (n = 40) all pts had possible Tx related adverse events (TRAEs; Table): diarrhoea (68%) and elevated alanine aminotransferase (ALT; 58%) were the most common TRAEs; elevated ALT (20%) and aspartate aminotransferase (15%) were the most common TRAEs leading to discontinuation. PK were as expected, inhibition of soluble PD-L1 was observed in all pts and no Tx emergent ADAs were observed. In Arms 1 + 1a, most patients achieved objective response (63.3%; 95% confidence intervals [CI]: 43.9, 80.1), median duration of response was 9.2 months (95% CI: 3.7, 14.0) and median progression-free survival (mPFS) was 10.1 months (95% CI: 5.5, 15.2; Table). PD-L1 expression ≥20% was associated with numerical improvements in mPFS (Table).
Conclusions
G + D had a high discontinuation rate due to liver related TRAEs and there was no additional benefit vs historical data for G alone. However, tumours expressing PD-L1 had favourable PFS and could be investigated further.
Clinical trial identification
NCT02088112; March 14, 2014.
Editorial acknowledgement
Medical writing support, under the direction of the authors, was provided by Lauren McNally, MSci, of CMC CONNECT, a division of McCann Health Medical Communications Ltd, Glasgow, UK, with funding from AstraZeneca PLC, in accordance with Good Publication Practice (GPP3) guidelines.
Legal entity responsible for the study
MedImmune LLC (a wholly owned subsidiary of AstraZeneca PLC).
Funding
AstraZeneca PLC.
Disclosure
T. Yeh, W. Tang, M. Tang, H.K. Angell, M.P. Roudier, M. Marotti: Employee: AstraZeneca. R. Taylor: Employee, contractor: AstraZeneca. D.L. Gibbons: Advisory boards/research funding: AstraZeneca. All other authors have declared no conflicts of interest.
104O - IMpower150: An exploratory analysis of efficacy outcomes in patients with EGFR mutations
- M. Reck (Grosshansdorf, Germany)
- M. Reck (Grosshansdorf, Germany)
- R. Jotte (Denver, CO, United States of America)
- T. Mok (Shatin, Hong Kong PRC)
- D. Lim (Singapore, Singapore)
- F. Cappuzzo (Ravenna, Italy)
- F. Orlandi (Santiago, Chile)
- D. Stroyakovskiy (Moscow, Russian Federation)
- N. Nogami (Matsuyama, Japan)
- D. Rodríguez-Abreu (Las Palmas, Spain)
- D. Moro-Sibilot (Grenoble, France)
- C. Thomas (Scarborough, ME, United States of America)
- F. Barlesi (Marseille, CEDEX 20, France)
- G. Finley (Pittsburgh, PA, United States of America)
- M. Nishio (Tokyo, Japan)
- A. Lee (South San Francisco, CA, United States of America)
- G. Shankar (South San Francisco, CA, United States of America)
- W. Yu (South San Francisco, CA, United States of America)
- M. Socinski (Orlando, FL, United States of America)
Abstract
Background
Atezolizumab (atezo; anti–PD-L1) inhibits PD-L1 to restore anticancer immunity; bevacizumab (bev) may enhance atezo efficacy by inhibiting VEGF immunosuppression and promoting T-cell tumour infiltration. Atezo + bev + chemotherapy (chemo) prolonged PFS and OS vs bev + CP in pts with first-line nonsquamous NSCLC in the randomised Ph III IMpower150 study, including pts with EGFR or ALK genomic alterations. The purpose of this analysis is to focus on the efficacy of atezo and/or bev with chemo in pts with EGFR mutations (EGFR-mt).
Methods
The 1202 enrolled pts received atezo (A) 1200 mg + bev (B) 15 mg/kg + carboplatin (C) AUC 6 + paclitaxel (P) 200 mg/m2 (ABCP) or A + C + P (ACP) or B + C + P (BCP) by IV q3w for 4 or 6 cycles per investigator (INV) decision, then q3w maintenance with atezo + bev, atezo or bev, respectively. Primary endpoints were OS and INV-assessed PFS in the ITT–wild-type population (pts with no EGFR or ALK genomic alterations). Exploratory analyses included OS and INV-assessed PFS in pts with EGFR-mt disease, pts with sensitising EGFR-mt and pts with EGFR-mt disease with prior TKI therapy.
Results
These data represent ≥ 20-mo follow-up (data cutoff: 22 Jan 2018) in the ITT population. 124 pts were EGFR-mt; 91 with a sensitising mutation. Baseline characteristics of EGFR-mt pts across treatment arms were generally comparable to the ITT population. OS was improved with ABCP vs BCP in EGFR-mt pts, especially in pts with sensitising EGFR-mts (HR, 0.31 [95% CI: 0.11, 0.83]). This benefit extended to PFS (HR, 0.41 [95% CI: 0.23, 0.75]). See table for full efficacy results. Safety was similar between the EGFR-mt and ITT populations.
Conclusions
IMpower150 is the first randomised Ph III trial of a checkpoint inhibitor to show a benefit in pretreated EGFR-mt pts. Adding atezo to standard-of-care bev and chemo provided survival benefit in EGFR-mt pts who have failed TKIs, for whom this regimen may represent a new treatment option.
Clinical trial identification
NCT02366143.
Editorial acknowledgement
Medical writing assistance for this abstract was provided by Jessica Men, PharmD, of Health Interactions and funded by F. Hoffmann-La Roche, Ltd.
Legal entity responsible for the study
F. Hoffmann-La Roche, Ltd.
Funding
F. Hoffmann-La Roche, Ltd.
Disclosure
M. Reck: Speakers bureau, consulting, advisory role: Roche, Lilly, Pfizer, BI, AZ, MSD, BMS, Merck, Novartis, Celgene; Other (support of parent study, funding of editorial support): Roche. R. Jotte: Speakers bureau; travel, accommodations, expenses: Bristol-Myers Squibb; Other (support of parent study, funding of editorial support): Roche. T.S.K. Mok: Honoraria, consult/ad role, research: AZ, BI, BMS, Merck, NVS, Pfizer, Roche/GNE; Honoraria, consult/ad role: LLY; Consult/Ad Role: ACEA, Celgene, geneD, Ignyta, OGXI, Vertex; Consult/ad role, research: Clovis, SFJ; Research: Eisai, Taiho; Stock: Sanomics, Hutch. D.W-T. Lim: Honoraria: AZ, BI, Novartis, MSD, Pfizer, Roche, Takeda, Taiho; Research grants (institution): BMS; Stock: Clearbridge Biomedics Pte Ltd, Mesh Bio Pte Ltd; Other (support of parent study, funding of editorial support): Roche. F. Cappuzzo: Speakers/Advisory board: Roche, AZ, BMS, Pfizer, MSD, Takeda; Other (support of parent study, funding of editorial support): Roche. F. Orlandi: Consult/ad role: AZ, Lilly; Consult/ad role, travel, research: Roche, BMS, MSD; Consult/ad role, travel: Pfizer; Speaker, travel, research: MedImm; Research: Amgen, BI, Astellas, Celltrion. D. Stroyakovskiy, C.A. Thomas: Support of parent study, funding of editorial support: Roche. N. Nogami: Honoraria: AZ, Pfizer, Ono Pharmaceutical, Kyowa Hakko Kririn, Taiho, Chugai, Eli Lilly, BI, MSD; Other (support of parent study and funding of editorial support): Roche. D. Rodríguez-Abreu: Speakers bureau: MSD, Roche, BMS, AZ, Pfizer; Other (support of parent study and funding of editorial support): Roche. D. Moro-Sibilot: Honoraria; Consulting/advisory role, travel, accommodations, expenses: Roche, MSD, Pfizer, BMS, AZ; Honoraria, consulting/advisory role: Novartis, Lilly; Other (support of parent study, funding of editorial support): Roche. F. Barlesi: Support of parent study, funding of editorial support: Roche; Personal fees: AZ, BMS, BI, Clovis, Lilly, Roche, Novartis, Merck, MSD, Pierre Fabre, Pfizer, Takeda; Consulting/advisory: MSD, Takeda. G. Finley: Speakers: BMS, BI, Astellas Medivation, Merck; Support of parent study, funding of editorial support: Roche. M. Nishio: Speakers/Ad board, research grant: Ono Pharma, BMS, Pfizer, Chugai, Lilly, Taiho, AZ, MSD, Novartis; Speakers/Ad board: BI, Sankyo, Merck; Research Grant: Astellas; Support of parent study, funding of editorial support: Roche. A. Lee: Employee/Stock: Genentech; Support of parent study, funding of editorial support: Roche. G. Shankar, W. Yu: Employee: Genentech; Support of parent study, funding of editorial support: Roche. M.A. Socinski: Honoraria/speakers bureau/research funding: Genentech; Support of parent study, funding of editorial support: Roche.
105O - Osimertinib for patients (pts) with leptomeningeal metastases (LM) associated with EGFRm advanced NSCLC: The AURA LM study
- M. Ahn (Seoul, Korea, Republic of)
- M. Ahn (Seoul, Korea, Republic of)
- C. Chiu (Taipei, Taiwan)
- Y. Cheng (Changchun, Jilin, China)
- J. Han (Goyang, KR, Korea, Republic of)
- S. Goldberg (New Haven, United States of America)
- A. Greystoke (Newcastle-upon-Tyne, Tyne and Wear, United Kingdom)
- J. Crawford (Durham, NC, United States of America)
- Y. Zhao (Zhengzhou, China)
- X. Huang (Cambridge, United Kingdom)
- M. Johnson (Cambridge, United Kingdom)
- K. Vishwanathan (Waltham, United States of America)
- A. Mendoza-Naranjo (Cambridge, United Kingdom)
- T. Mok (Shatin, Hong Kong PRC)
Abstract
Background
Osimertinib, a 3rd-generation EGFR-TKI selective for both sensitising and EGFR T790M resistance mutations, has shown efficacy in pts with CNS metastases; encouraging activity has been reported in pts with LM at 160 mg once daily (QD) (BLOOM; NCT02228369). We report LM activity with osimertinib 80 mg QD in pts with LM from studies across the AURA program (NCT01802632; NCT02094261; NCT02442349; NCT02151981).
Methods
Pts with EGFR T790M positive advanced NSCLC and progression on EGFR-TKI received osimertinib 80 mg QD. Patients with LM and CNS metastases were eligible if asymptomatic and stable. Baseline brain scans were mandated in pts with known or treated CNS metastases at study entry; pts with evidence of LM by neuroradiological blinded independent review (BICR) were included for retrospective analysis. Follow-up brain scans were assessed for radiologic LM response by LM BICR per Response Assessment in Neuro-Oncology LM criteria. LM objective response rate (ORR), LM duration of response (DoR), LM progression-free survival (PFS) and overall survival (OS) were assessed retrospectively. Results are based on individual data cutoffs for each study. A longitudinal analysis overlaid changes from baseline non-CNS tumour size with LM responses at each visit for AURA LM and BLOOM LM pts.
Results
22 LM pts from the AURA studies were included for analysis. Median treatment exposure was 7.3 mo (range 2.3–16.5). Baseline characteristics were broadly consistent with the overall AURA study population: median age 58 yrs; female 59%; Asian 82%; WHO PS 1 82%. LM ORR was 55% (95% CI 32, 76); complete or partial LM response reported in 6 pts (27%) each. Median LM DoR was not reached (95% CI 2.8, not calculable [NC]). Median LM PFS was 11.1 mo (95% CI 4.6, NC). OS was 18.8 mo (95% CI 6.3, NC). Graphical assessment of longitudinal analysis showed similar non-CNS and LM responses in AURA LM and BLOOM LM pts.
Conclusions
Consistent with early efficacy outputs from BLOOM (160mg QD), osimertinib 80 mg QD showed a clinically meaningful benefit in pts with T790M-positive NSCLC and radiographically-detected LM. Additional studies are needed to further evaluate the CNS efficacy of osimertinib 80 mg QD in pts with EGFRm NSCLC and LM.
Clinical trial identification
AURA extension (NCT01802632), AURA2 (NCT02094261), AURA3 (NCT02151981), AURA17 (NCT02442349).
Editorial acknowledgement
Medical support was provided by Robert Harrison, PhD, of iMed Comms, Macclesfield, UK, an Ashfield Company, part of UDG Healthcare plc, and funded by AstraZeneca, Cambridge, UK, in accordance with Good Publications Practice (GPP3) guidelines.
Legal entity responsible for the study
AstraZeneca.
Funding
AstraZeneca.
Disclosure
M-J. Ahn: Speakers’ bureau: AstraZeneca, MSD, ONO, Lilly, Roche; Consultant: Alpha Pharmaceutical. C-H. Chiu: Honorarium: AZ, BI, Novartis, Pfizer, Roche. J-Y. Han: Honoraria: Roche, AstraZeneca, BMS, MSD; Advisory role: AstraZeneca, BMS, MSD, Lilly, Novartis, Pfizer; Research fund: Roche, Pfizer, ONO. S.B. Goldberg: Research support: AstraZeneca; Advisory board member: AstraZeneca, Boehringer Ingelheim, Eli Lilly, Bristol-Myers Squibb, Genentech, Amgen, Spectrum. A. Greystoke: Consultancy fees, speaker fees: AstraZeneca. J. Crawford: Scientific advisor: Amgen, Enzychem, Merck, Pfizer; Consultant: Amgen, AstraZeneca, Coherus, Enzychem, Merck, Pfizer; Research support: AstraZeneca, Genentech, Helsinn; Chair/DSMB member: Beyond Spring, G1 Therapeutics, Janssen, Merrimack, Mylan, Roche. X. Huang, M. Johnson, K. Vishwanathan, A. Mendoza-Naranjo: Employee, shareholder: AstraZeneca. T.S.K. Mok: Leadership (for-profit): ChiMed, Sanomics Ltd.; Leadership (non-profit): IASLC, ASCO, Chinese Society of Clinical Oncology; Shareholder: Sanomics Ltd.; Honoraria: AZ, BI, Roche/Genentech, Pfizer, Lilly, Merck Serono, MSD, Novartis, SFJ, ACEA, Vertex, BMS, Oncogenex, Celgene, Ignyta, Cirina, Fishawack Facilitate, Takeda Oncology, Janssen, ChiMed; Consulting/advisory role: AZ, BI, Roche/Genentech, Pfizer, Lilly, Merck Serono, MSD, Novartis, SFJ Company, ACEA, Vertex, BMS, GeneDecode, Oncogenex, Celgene, Ignyta, Cirina, Fishawack Facilitate, Janssen, Takeda Oncolog, ChiMed; Research funding: AZ, BI, Pfizer, Novartis, SFJ, Roche, MSD, Clovis Oncology, BMS, Eisai, Taiho, Merck Serono, XCovery. All other authors have declared no conflicts of interest.
Invited Discussant 84O, 104O and 105O
- P. Jänne (Boston, MA, United States of America)
- P. Jänne (Boston, MA, United States of America)
106O - Brigatinib (BRG) vs crizotinib (CRZ) in the phase III ALTA-1L trial
- R. Califano (Manchester, United Kingdom)
- R. Califano (Manchester, United Kingdom)
- M. Hochmair (Vienna, Austria)
- C. Gridelli (Avellino, Italy)
- A. Delmonte (Meldola, Italy)
- M. Garcia Campelo (Coruna, Spain)
- A. Bearz (Aviano, Italy)
- F. Griesinger (Oldenburg, Germany)
- A. Morabito (Naples, Italy)
- E. Felip (Barcelona, Spain)
- S. Ghosh (London, United Kingdom)
- M. Tiseo (Parma, Italy)
- J. Haney (Cambridge, MA, United States of America)
- D. Kerstein (Cambridge, MA, United States of America)
- S. Popat (London, United Kingdom)
- D. Camidge (Aurora, CO, United States of America)
Abstract
Background
We report results of the first interim analysis (IA) from the ALTA-1L study of BRG vs CRZ in anaplastic lymphoma kinase (ALK) inhibitor–naive, ALK-positive non–small cell lung cancer (ALK+ NSCLC; NCT02737501).
Methods
This open-label, multicenter study enrolled patients (pts) with advanced ALK+ NSCLC. Eligible pts had ≤1 prior systemic therapy for advanced NSCLC. Asymptomatic central nervous system (CNS) metastases were allowed. Pts were randomized 1:1 to BRG 180 mg QD with 7-day lead-in at 90 mg or CRZ 250 mg BID. Primary endpoint was blinded independent review committee (BIRC)-assessed progression-free survival (PFS; RECIST v1.1); secondary efficacy endpoints included BIRC-assessed objective response rate (ORR), intracranial ORR (iORR), and intracranial PFS (iPFS). IAs were planned at 50% and 75% of 198 expected PFS events.
Results
275 pts were randomized (BRG/CRZ, n = 137/138); median age (years) 58/60. 26%/27% received prior chemotherapy for advanced disease, and 29%/30% had baseline brain metastases. At data cutoff (19 Feb 2018), with a median follow-up of 11.0/9.3 months (BRG/CRZ) and 99 PFS events, BRG met the prespecified threshold for statistical superiority vs CRZ in the primary endpoint of BIRC-assessed PFS (HR 0.49; 95% CI, 0.33–0.74; log-rank P = 0.0007); BRG median PFS was not reached (NR; 95% CI, NR) vs CRZ 9.8 months (95% CI, 9.0–12.9). Investigator-assessed PFS HR 0.45 (95% CI, 0.30–0.68); log-rank P = 0.0001. Table shows additional efficacy data. Most common grade ≥3 treatment-emergent adverse events (AEs): BRG: increased blood creatine phosphokinase (16.2%) and lipase (13.2%), hypertension (9.6%); CRZ: increased alanine aminotransferase (9.5%), aspartate aminotransferase (5.8%), and lipase (5.1%). Any grade interstitial lung disease/pneumonitis: BRG, 3.7%; CRZ, 2.2%. Discontinuations due to AE (BRG/CRZ): 11.8%/8.8%.
Conclusions
BRG showed a statistically and clinically significant improvement in PFS vs CRZ in ALK inhibitor–naive ALK+ NSCLC.
Clinical trial identification
NCT02737501.
Editorial acknowledgement
Professional medical writing assistance was provided by Lauren Gallagher, PhD, (Peloton Advantage, Parsippany, NJ) and funded by Millennium Pharmaceuticals, Inc.
Legal entity responsible for the study
ARIAD Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
Funding
ARIAD Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
Disclosure
R. Califano: Honoraria, consulting/advisory role: AstraZeneca, BMS, Roche, MSD, Boehringer Ingelheim, Takeda, Novartis, Pfizer, Lilly Oncology. C. Gridelli: Speakers bureau, advisory role: Pfizer, Roche. A. Delmonte: Consulting/advisory role: AstraZeneca, Boehringer Ingelheim. M.R. Garcia Campelo: Honoraria: ARIAD, AstraZeneca, Roche, Pfizer, BMS, Boehringer Ingelheim; Speakers bureau, advisory role: ARIAD, AstraZeneca, Roche, Pfizer, BMS, Boehringer Ingelheim. A. Bearz: Speakers bureau, advisory role: AstraZeneca, Pfizer, Eli Lilly, BMS, Novartis, Roche, MSD, Boehringer Ingelheim, Takeda. F. Griesinger: Research funding to institution: AstraZeneca, Boehringer Ingelheim, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, Takeda, Siemens; Consulting or advisory role: ARIAD, AstraZeneca, Boehringer Ingelheim, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, Takeda, ARIAD, AbbVie, Siemens. E. Felip: Consulting/advisory role: AbbVie, AstraZeneca, Blue Print Medicines, Boehringer Ingelheim, BMS, Celgene, Eli Lilly, Guardant Health, Janssen, Merck KGaA, MSD, Novartis, Pfizer, Roche, Takeda; Speakers bureau: AbbVie, AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, Merck KGaA, MSD, Novartis, Pfizer, Roche, Takeda. S. Popat: Research funding to institution: Boehringer Ingelheim, Epizyme, BMS, Clovis Oncology, Roche, Lilly, Takeda; Honoraria: Boehringer Ingelheim, AstraZeneca, Roche, Takeda, Chugai Pharma; Consulting or advisory role: Boehringer Ingelheim, Roche, Novartis, Pfizer, AstraZeneca, BMS, MSD, Guardant Health, AbbVie; Travel, accommodations, expenses: Boehringer Ingelheim, BMS, Merck Sharp & Dohme. A. Morabito: Honoraria: AstraZeneca, Roche, Boehringer Ingelheim, Pfizer, MSD, BMS. S. Ghosh: Honoraria/speakers bureau: Pfizer. M. Tiseo: Speakers bureau, advisory role: AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, MSD, Novartis, Otsuka, Pfizer, Pierre Fabre, Roche. J. Haney, D. Kerstein: Employment, stock and other ownership interests: Arîad. D.R. Camidge: Honoraria: AstraZeneca, Takeda, Arrys/Kyn, Genoptix, G1 Therapeutics (DSMB), Mersana Therapeutics, Roche/Genentech, Ignyta, Daichii Sankyo (ILD adjudication committee), Hansoh SRC, Bio-Thera DSMB, Lycera, Revolution Med, Orion, Clovis, Celgene, Novartis); Research funding (ARIAD/Takeda). All other authors have declared no conflicts of interest.
107O - Crizotinib in advanced ROS1-rearranged non-small cell lung cancer (NSCLC): Overall survival (OS) and updated safety from PROFILE 1001
- A. Shaw (Boston, MA, United States of America)
- A. Shaw (Boston, MA, United States of America)
- G. Riely (New York, NY, United States of America)
- Y. Bang (Seoul, Korea, Republic of)
- D. Kim (Seoul, Korea, Republic of)
- D. Camidge (Aurora, CO, United States of America)
- G. Shapiro (Boston, MA, United States of America)
- T. Usari (Milano, Italy)
- S. Wang (La Jolla, CA, United States of America)
- K. Wilner (San Diego, United States of America)
- J. Clark (Boston, MA, United States of America)
- S. Ou (Orange, CA, United States of America)
Abstract
Background
In the ongoing phase 1 PROFILE 1001 study (NCT00585195), crizotinib provided a meaningful clinical benefit for patients (pts) with advanced ROS1-rearranged NSCLC, as evidenced by a high objective response rate (72%) and rapid, substantial and durable responses (median duration of response, 18 months [mo]); in addition, crizotinib was well-tolerated (Shaw, N Engl J Med, 2014). Here, we present OS results and updated safety (additional follow-up >3 years) in these pts.
Methods
Pts with histologically confirmed NSCLC containing ROS1 rearrangements were enrolled and treated with oral crizotinib 250 mg twice daily (BID). ROS1 status was assessed by fluorescence in situ hybridization or reverse transcriptase polymerase chain reaction.
Results
Between October 2010 and June 2018, 53 pts with ROS1-rearranged NSCLC were treated with crizotinib; median duration of treatment was 22 mo (95% confidence interval [CI]: 15, 36). At the time of data cutoff (June 30, 2018), 12 pts (22.6%) remained on treatment. A total of 26 deaths (49.1%) occurred over a median follow-up period of 63 mo. Median OS was 51 mo (95% CI: 29, not reached) and the probabilities of survival at 12, 24 and 48 mo were 78.8%, 67.0% and 50.7%, respectively. With a median treatment duration nearly 8 mo longer than that for the primary endpoint analysis and 30.2% of patients on treatment for more than 4 years, no new safety signals were noted. The most common grade 3 treatment-related adverse events (TRAEs; in ≥ 5% of pts) were hypophosphatemia (15.1%) and neutropenia (9.4%); no grade 4 TRAEs or treatment-related deaths were reported. With longer follow-up, there were no permanent discontinuations associated with TRAEs.
Conclusions
The results of the OS analysis and updated safety information from PROFILE 1001 continue to support the favorable benefit/risk profile of crizotinib 250 mg BID for the treatment of patients with advanced ROS1-positive NSCLC.
Clinical trial identification
NCT00585195.
Editorial acknowledgement
Editorial assistance was provided by Vasupradha Vethantham, PhD, of inScience Communications, Springer Healthcare (New York, NY, USA), with funding from Pfizer, Inc.
Legal entity responsible for the study
Pfizer, Inc.
Funding
Pfizer, Inc.
Disclosure
A. Shaw: Fees for consulting/advisory board roles: ARIAD/Takeda, Blueprint Medicines, Daiichi Sankyo, EMD Serono, Foundation Medicine Genentech, Ignyta, KSQ Therapeutics, Loxo, Novartis, Pfizer, Roche, Taiho; Honoraria: Novartis, Pfizer, Roche; Research funding to institution: Daiichi Sankyo, Ignyta, Novartis, Pfizer, Roche/Genentech, TP Therapeutics. Y-J. Bang: Advisory boards: Astellas, AstraZeneca, Bayer, BeiGene, Bristol-Myers Squibb, Daiich-Sankyo, Eli Lilly, GreenCross, Genentech/Roche, Hanmi, Novartis, Merck Serano, MSD, Samyang Biopharm, Taiho; Research funding to institution: Astellas, AstraZeneca, Bayer, BeiGene, Bristol-Myers Squibb, Boeringer Ingelheim, Boston Biomedical, CKD Pharma, Curis, Daiichi Sankyo, Eli Lilly, FivePrime, Glaxo Smith-Kline, Genentech/Roche, Green Cross, MacroGenics, Merck Serano, MSD, Novartis, Pfizer, Ono, Takeda, Taiho. D.R. Camidge: Advisory boards: AbbVie, ARIAD, Array, Celgene, Clovis, Eli Lilly, G1 Therapeutics (DSMB), Genoptix, Ignyta, Mersana Therapeutics, Novartis, Orion, Roche/Genentech, Takeda; Research for investigator-initiated trials: ARIAD, Takeda. G.J. Riely: Funding to institution: Pfizer for the conduct of this research; Research support to institution: Novartis, Roche, Takeda. Compensated consultant: Genentech/Roche. G.I. Shapiro: Research funding to the Dana-Farber Cancer Institute: Pfizer for the conduct of the study; Advisory boards: Eli Lilly, G1 Therapeutics, Merck/EMD Serono, Roche, Pfizer, Vertex Pharmaceuticals. T. Usari, S.C. Wang, K. Wilner: Employee, holds stock: Pfizer. J.W. Clark: Institutional research funding: Pfizer. S-H.I. Ou: Fees for consulting/Advisory board: Pfizer; Research funding to institution: Eli Lilly, Merck/EMD Serono, Pfizer. All other authors have declared no conflicts of interest.
Invited Discussant 106O and 107O
- N. Leighl (Toronto, Canada)
- N. Leighl (Toronto, Canada)