Malignant solid neoplasm, ERBB2-mutated

4 regimens on this page 4 variants on this page

Note: this is a new type of page for HemOnc.org, as most other regimen pages are tissue-specific. We will collect published information from basket trials on these pages, as well as regimens that are FDA approved.

All lines of therapy

Ado-trastuzumab emtansine monotherapy

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Regimen

Study	Evidence
Li et al. 2018 (MSK 15-335)	Phase II basket trial, <20 pts reported to date

Note: only partial results have been published to date.

Biomarker eligibility criteria

• Gene: HER2
• Alteration: various exon 20 insertions, single-base pair substitutions, or other likely activating mutations
• Acceptable methods of measurement: next-generation sequencing

Chemotherapy

• Ado-trastuzumab emtansine (Kadcyla) 3.6 mg/kg IV once on day 1

21-day cycles

References

1. MSK 15-335: Li BT, Shen R, Buonocore D, Olah ZT, Ni A, Ginsberg MS, Ulaner GA, Offin M, Feldman D, Hembrough T, Cecchi F, Schwartz S, Pavlakis N, Clarke S, Won HH, Brzostowski EB, Riely GJ, Solit DB, Hyman DM, Drilon A, Rudin CM, Berger MF, Baselga J, Scaltriti M, Arcila ME, Kris MG. Ado-trastuzumab emtansine for patients with HER2-mutant lung cancers: results from a phase II basket trial. J Clin Oncol. 2018 Aug 20;36(24):2532-2537. Epub 2018 Jul 10. link to original article contains verified protocol PubMed

Neratinib monotherapy

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Regimen

Study	Evidence
Hyman et al. 2018 (SUMMITHER)	Non-randomized basket trial

Note: the cycle length is not described in the manuscript; the authors have clarified that the cycles are 28 days in length. This trial should not be confused with the one by the same name in multiple myeloma.

Biomarker eligibility criteria

• Gene: HER2
• Alteration: various substitutions, insertions, frameshifts, or structural variants
• Acceptable methods of measurement: next-generation sequencing assay or RT-PCR, Sanger, pyrosequencing, or mass spectrometry-based sequencing methods

Preceding treatment

• No prior treatment with HER kinase inhibitors

Chemotherapy

• Neratinib (Nerlynx) 240 mg PO once per day

Supportive medications

• Loperamide (Imodium) (dose not specified) mandatory during cycle 1

28-day cycles

References

1. SUMMIT: Hyman DM, Piha-Paul SA, Won H, Rodon J, Saura C, Shapiro GI, Juric D, Quinn DI, Moreno V, Doger B, Mayer IA, Boni V, Calvo E, Loi S, Lockhart AC, Erinjeri JP, Scaltriti M, Ulaner GA, Patel J, Tang J, Beer H, Selcuklu SD, Hanrahan AJ, Bouvier N, Melcer M, Murali R, Schram AM, Smyth LM, Jhaveri K, Li BT, Drilon A, Harding JJ, Iyer G, Taylor BS, Berger MF, Cutler RE Jr, Xu F, Butturini A, Eli LD, Mann G, Farrell C, Lalani AS, Bryce RP, Arteaga CL, Meric-Bernstam F, Baselga J, Solit DB. HER kinase inhibition in patients with HER2- and HER3-mutant cancers. Nature. 2018 Feb 8;554(7691):189-194. Epub 2018 Jan 31. link to original article contains verified protocol link to PMC article PubMed

Pertuzumab & Trastuzumab

Regimen

Study	Evidence
Hainsworth et al. 2018 (MyPathway)	Phase IIa

Biomarker eligibility criteria

• Gene: HER2
• Alteration: amplification or activation (including exon 20 insertions, deletions around amino acids 755 to 759, and nonsynonymous amino acid substitutions)
• Acceptable methods of measurement: molecular profiling performed on tissue obtained at the most recent tumor biopsy

Chemotherapy

• Pertuzumab (Perjeta) as follows:
  • Cycle 1: 840 mg IV once on day 1
  • Cycle 2 onwards: 240 mg IV once on day 1
• Trastuzumab (Herceptin) as follows:
  • Cycle 1: 8 mg/kg IV once on day 1
  • Cycle 2 onwards: 6 mg/kg IV once on day 1

21-day cycles

References

1. MyPathway: Hainsworth JD, Meric-Bernstam F, Swanton C, Hurwitz H, Spigel DR, Sweeney C, Burris H, Bose R, Yoo B, Stein A, Beattie M, Kurzrock R. Targeted therapy for advanced solid tumors on the basis of molecular profiles: results from MyPathway, an open-label, phase IIa multiple basket study. J Clin Oncol. 2018 Feb 20;36(6):536-542. Epub 2018 Jan 10. link to original article contains verified protocol PubMed