Pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer (MyPathway)

an updated report from a multicentre, open-label, phase 2a, multiple basket study

Funda Meric-Bernstam, Herbert Hurwitz, Kanwal Pratap Singh Raghav, Robert R. McWilliams, Marwan Fakih, Vanderwalde Ari, Charles Swanton, Razelle Kurzrock, Howard Burris, Christopher Sweeney, Ron Bose, David R. Spigel, Mary S. Beattie, Steven Blotner, Alyssa Stone, Katja Schulze, Vaikunth Cuchelkar, John Hainsworth

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)518-530
Number of pages13
JournalThe Lancet Oncology
Volume20
Issue number4
DOIs
StatePublished - Apr 1 2019

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Colorectal Neoplasms
Therapeutics
pertuzumab
Trastuzumab
Chills
Hypokalemia
Nausea
Abdominal Pain
Stomach Neoplasms
Fatigue
Diarrhea
Neoplasms
Cohort Studies
Research Personnel
Breast Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer (MyPathway) : an updated report from a multicentre, open-label, phase 2a, multiple basket study. / Meric-Bernstam, Funda; Hurwitz, Herbert; Raghav, Kanwal Pratap Singh; McWilliams, Robert R.; Fakih, Marwan; Ari, Vanderwalde; Swanton, Charles; Kurzrock, Razelle; Burris, Howard; Sweeney, Christopher; Bose, Ron; Spigel, David R.; Beattie, Mary S.; Blotner, Steven; Stone, Alyssa; Schulze, Katja; Cuchelkar, Vaikunth; Hainsworth, John.

In: The Lancet Oncology, Vol. 20, No. 4, 01.04.2019, p. 518-530.

Research output: Contribution to journalArticle

Meric-Bernstam, F, Hurwitz, H, Raghav, KPS, McWilliams, RR, Fakih, M, Ari, V, Swanton, C, Kurzrock, R, Burris, H, Sweeney, C, Bose, R, Spigel, DR, Beattie, MS, Blotner, S, Stone, A, Schulze, K, Cuchelkar, V & Hainsworth, J 2019, 'Pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer (MyPathway): an updated report from a multicentre, open-label, phase 2a, multiple basket study', The Lancet Oncology, vol. 20, no. 4, pp. 518-530. https://doi.org/10.1016/S1470-2045(18)30904-5
Meric-Bernstam, Funda ; Hurwitz, Herbert ; Raghav, Kanwal Pratap Singh ; McWilliams, Robert R. ; Fakih, Marwan ; Ari, Vanderwalde ; Swanton, Charles ; Kurzrock, Razelle ; Burris, Howard ; Sweeney, Christopher ; Bose, Ron ; Spigel, David R. ; Beattie, Mary S. ; Blotner, Steven ; Stone, Alyssa ; Schulze, Katja ; Cuchelkar, Vaikunth ; Hainsworth, John. / Pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer (MyPathway) : an updated report from a multicentre, open-label, phase 2a, multiple basket study. In: The Lancet Oncology. 2019 ; Vol. 20, No. 4. pp. 518-530.
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abstract = "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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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 - Ari, Vanderwalde

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

PY - 2019/4/1

Y1 - 2019/4/1

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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