TY - JOUR
T1 - Pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer (MyPathway)
T2 - an updated report from a multicentre, open-label, phase 2a, multiple basket study
AU - Meric-Bernstam, Funda
AU - Hurwitz, Herbert
AU - Raghav, Kanwal Pratap Singh
AU - McWilliams, Robert R.
AU - Fakih, Marwan
AU - VanderWalde, Ari
AU - Swanton, Charles
AU - Kurzrock, Razelle
AU - Burris, Howard
AU - Sweeney, Christopher
AU - Bose, Ron
AU - Spigel, David R.
AU - Beattie, Mary S.
AU - Blotner, Steven
AU - Stone, Alyssa
AU - Schulze, Katja
AU - Cuchelkar, Vaikunth
AU - Hainsworth, John
N1 - Funding Information:
We thank the patients, families, and study teams who participated in MyPathway. We also thank Bongin Yoo (Genentech, South San Francisco, CA, USA) for his work on the statistical analysis, Yong Wang (Genentech, South San Francisco, CA, USA) for her programming support, Rajesh Patel (Genentech, South San Francisco, CA, USA) for his assistance with the validation of the molecular profiling data, and Hiro Nitta (Ventana, Tucson, AZ, USA) and Bryce Portier (Ventana, Tucson, AZ, USA) for the performance of the HER2 gene protein assay. The MyPathway study was designed by the Sarah Cannon Research Institute and F Hoffmann-La Roche/Genentech in collaboration with the study Steering Committee and was funded by F Hoffmann-La Roche/Genentech. Third-party writing assistance was provided by Sabrina Hom (CodonMedical, Ashfield) and was funded by F Hoffmann-La Roche/Genentech. This work was also supported in part by The Cancer Prevention and Research Institute of Texas (RP1100584), the Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy, NCATS Grant UL1 TR000371 ( Center for Clinical and Translational Sciences ), and the MD Anderson Cancer Center Support Grant ( P30 CA016672 ).
Funding Information:
FM-B has served as a consultant for Dialecta and Sumitomo Dainippon; has served on advisory committees for Inflection Biosciences, Pieris, and DarwinHealth; and has received research funding from Aileron Therapeutics, AstraZeneca, Bayer, Calithera Biosciences, CytomX Therapeutics, Debiopharm Group, Genentech, Novartis, PUMA Biotechnology, Zymeworks, Pfizer, Jounce, eFFECTOR, Curis, AbbVie, and Taiho Pharmaceutical. HH is employed by and owns stock in Roche/Genentech; has served as a consultant for Acceleron Pharma, Bristol-Myers Squibb, Roche/Genentech, GlaxoSmithKline, Incyte, Lilly, Novartis, OncoMed, and TRACON Pharma; has received honoraria from Roche/Genentech and Lilly/ImClone; and has received travel, accommodation, and expense reimbursement from Roche/Genentech and TRACON Pharmaceuticals. HH's former institution (Duke University Medical Center, Durham, NC, USA) received research funding from Bristol-Myers Squibb, Roche/Genentech, GlaxoSmithKline, Lilly, Macrogenics, NCI, Novartis, Regeneron, and TRACON Pharma. RRM has served on the advisory boards of Ipsen and Bristol-Myers Squibb. MF has served on advisory boards for Amgen, Array, Genentech, Merck, Taiho, Seattle Genetics, and Sirtex, and has received speaker fees from Amgen, Genentech, Sirtex, and Taiho and research support (paid to his institution) from Amgen, AstraZeneca, and Novartis. AV has received personal fees from AstraZeneca, Bristol-Myers Squibb, Roche/Genentech; grant funding from Amgen; and non-financial support from Caris Life Sciences. CSwa has received honoraria or consultant fees from Roche/Genentech, Ventana, Celgene, Pfizer, Novartis, and Bristol-Myers Squibb and grants from Pfizer and AstraZeneca, and owns stock in GRAIL, Epic Biosciences, Apogen Biotech, and Achilles Therapeutics (co-founder). RK has received grants from Incyte, Roche/Genentech, Merck Serono, Pfizer, Sequenom, Foundation Medicine, Guardant Health, and Konica Minolta and consulting fees from LOXO, X-Biotech, Actuate Therapeutics, Roche/Genentech, and NeoMed, and has an ownership interest in CureMatch. HB has received research funding for his institution from Roche/Genentech, Bristol-Myers Squibb, Incyte, Tarveda Therapeutics, Mersana Therapeutics, AstraZeneca, MedImmune, Macrogenics, Novartis, Boehringer Ingelheim, Eli Lilly, Seattle Genetics, AbbVie, Bayer, Celldex Therapeutics, Merck, Celgene, Agios Pharmaceuticals, and Jounce Therapeutics. CSwe has served as a consultant for Astellas Pharma, AstraZeneca, Bayer, Tolmar, Genentech/Roche, Janssen Biotech, and Sanofi; owns stock in Leuchemix; and has patents with Leuchemix and Exelixis. CSwe's institution has received research funding from Astellas Pharma, Exelixis, and Janssen Biotech. RB has served as a consultant for Roche/Genentech and has received honoraria from Genentech/Roche and Novartis and research funding from Puma Biotechnology. DRS has served as a consultant for and received travel, accommodations, and expense reimbursement from AstraZeneca, Biodesix, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Clovis Oncology, Roche/Genentech, Lilly, Novartis, and Pfizer; served on speakers' bureaus for Novartis; and owned stock in Foundation Medicine and Illumina. DRS's institution has received research funding from Amgen, Astex Pharmaceuticals, AstraZeneca, BIND Biosciences, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Clovis Oncology, CytRx Corporation, Daiichi Sankyo, EMD Serono, Genentech/Roche, ImClone Systems, Immunogen, Lilly, Novartis, Oncogenex, OncoMed, Peregrine Pharmaceuticals, Pfizer, University of Texas Southwestern Medical Center—Simmons Cancer Center, and Verastem. MSB, SB, AS, KS, and VC are employed by and own stock in Roche/Genentech. JH has received research funding for his institution from Astellas Pharma, AstraZeneca, Celgene, Roche/Genentech, Johnson & Johnson, Lilly, and Novartis. All authors received non-financial support from Roche in the form of medical writing support for this manuscript. KPSR declares no competing interests.
Publisher Copyright:
© 2019 Elsevier Ltd
PY - 2019/4
Y1 - 2019/4
N2 - Background: Therapies targeting HER2 have improved clinical outcomes in HER2-positive breast and gastric cancers, and are emerging as potential treatments for HER2-positive metastatic colorectal cancer. MyPathway evaluates the activity of targeted therapies in non-indicated tumour types with potentially predictive molecular alterations. We aimed to assess the activity of pertuzumab and trastuzumab in patients with HER2-amplified metastatic colorectal cancer. Methods: MyPathway is an ongoing, phase 2a, multiple basket study. Patients in this subset analysis were aged 18 years or older and had treatment-refractory, histologically confirmed HER2-amplified metastatic colorectal cancer with measurable or evaluable disease and an Eastern Cooperative Oncology Group performance status score of 2 or less, enrolled from 25 hospitals or clinics in 16 states of the USA. Patients received pertuzumab (840 mg loading dose, then 420 mg every 3 weeks, intravenously) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg every 3 weeks, intravenously). The primary endpoint was the proportion of patients who achieved an objective response based on investigator-reported tumour responses. Analyses were done per protocol. This ongoing trial is registered with ClinicalTrials.gov, number NCT02091141. Findings: Between Oct 20, 2014, and June 22, 2017, 57 patients with HER2-amplified metastatic colorectal cancer were enrolled in the MyPathway study and deemed eligible for inclusionin this cohort analysis. Among these 57 evaluable patients, as of Aug 1, 2017, one (2%) patient had a complete response and 17 (30%) had partial responses; thus overall 18 of 57 patients achieved an objective response (32%, 95% CI 20–45). The most common treatment-emergent adverse events were diarrhoea (19 [33%] of 57 patients), fatigue (18 [32%] patients), and nausea (17 [30%] patients). Grade 3–4 treatment-emergent adverse events were recorded in 21 (37%) of 57 patients, most commonly hypokalaemia and abdominal pain (each three [5%] patients). Serious treatment-emergent adverse events were reported in ten (18%) patients and two (4%) of these adverse events (ie, chills and infusion-related reaction) were considered treatment related. There were no treatment-related deaths. Interpretation: Dual HER2-targeted therapy with pertuzumab plus trastuzumab is well tolerated and could represent a therapeutic opportunity for patients with heavily pretreated, HER2-amplified metastatic colorectal cancer. Funding: F Hoffmann-La Roche/Genentech.
AB - Background: Therapies targeting HER2 have improved clinical outcomes in HER2-positive breast and gastric cancers, and are emerging as potential treatments for HER2-positive metastatic colorectal cancer. MyPathway evaluates the activity of targeted therapies in non-indicated tumour types with potentially predictive molecular alterations. We aimed to assess the activity of pertuzumab and trastuzumab in patients with HER2-amplified metastatic colorectal cancer. Methods: MyPathway is an ongoing, phase 2a, multiple basket study. Patients in this subset analysis were aged 18 years or older and had treatment-refractory, histologically confirmed HER2-amplified metastatic colorectal cancer with measurable or evaluable disease and an Eastern Cooperative Oncology Group performance status score of 2 or less, enrolled from 25 hospitals or clinics in 16 states of the USA. Patients received pertuzumab (840 mg loading dose, then 420 mg every 3 weeks, intravenously) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg every 3 weeks, intravenously). The primary endpoint was the proportion of patients who achieved an objective response based on investigator-reported tumour responses. Analyses were done per protocol. This ongoing trial is registered with ClinicalTrials.gov, number NCT02091141. Findings: Between Oct 20, 2014, and June 22, 2017, 57 patients with HER2-amplified metastatic colorectal cancer were enrolled in the MyPathway study and deemed eligible for inclusionin this cohort analysis. Among these 57 evaluable patients, as of Aug 1, 2017, one (2%) patient had a complete response and 17 (30%) had partial responses; thus overall 18 of 57 patients achieved an objective response (32%, 95% CI 20–45). The most common treatment-emergent adverse events were diarrhoea (19 [33%] of 57 patients), fatigue (18 [32%] patients), and nausea (17 [30%] patients). Grade 3–4 treatment-emergent adverse events were recorded in 21 (37%) of 57 patients, most commonly hypokalaemia and abdominal pain (each three [5%] patients). Serious treatment-emergent adverse events were reported in ten (18%) patients and two (4%) of these adverse events (ie, chills and infusion-related reaction) were considered treatment related. There were no treatment-related deaths. Interpretation: Dual HER2-targeted therapy with pertuzumab plus trastuzumab is well tolerated and could represent a therapeutic opportunity for patients with heavily pretreated, HER2-amplified metastatic colorectal cancer. Funding: F Hoffmann-La Roche/Genentech.
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U2 - 10.1016/S1470-2045(18)30904-5
DO - 10.1016/S1470-2045(18)30904-5
M3 - Article
C2 - 30857956
AN - SCOPUS:85063595326
SN - 1470-2045
VL - 20
SP - 518
EP - 530
JO - The lancet oncology
JF - The lancet oncology
IS - 4
ER -