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Comment
. 2022 May 5;386(18):1769-1770.
doi: 10.1056/NEJMc2202305.

Trastuzumab Deruxtecan in Non-Small-Cell Lung Cancer

Hollis Viray  1 , Deepa Rangachari  1 , Daniel B Costa  1
Affiliations
Comment

Trastuzumab Deruxtecan in Non-Small-Cell Lung Cancer

Hollis Viray et al. N Engl J Med. .
No abstract available

PubMed Disclaimer

Conflict of interest statement

Dr. Rangachari reports receiving consulting fees and honoraria from AstraZeneca, institutional research support from Bristol Myers Squibb, Novocure, and AbbVie/Stemcentrx, and consulting fees from Teladoc and DynaMed; and Dr. Costa, receiving consulting fees and honoraria from Takeda/Millennium Pharmaceuticals, AstraZeneca, Pfizer, Blueprint Medicines, and Janssen, institutional research support from Takeda/Millennium Pharmaceuticals, AstraZeneca, Pfizer, Merck Sharp and Dohme, Merrimack Pharmaceuticals, Bristol Myers Squibb, Clovis Oncology, Spectrum Pharmaceuticals, Tesaro, and Daiichi Sankyo, and consulting fees from Teladoc and Grand Rounds by Included Health. No other potential conflict of interest relevant to this letter was reported.

Figures

Figure 1.
Figure 1.. Three Patients with Lung Cancer with ERBB2 Exon 20 Mutations Who Received Trastuzumab Deruxtecan after Use of Poziotinib.
All the patients received poziotinib at varying doses as part of the ongoing ZENITH20 trial, and this portion of their cancer care has been reported previously.- Patient 1, who had lung adenocarcinoma with an ERBB2 P780_Y781insGSP mutation, had received carboplatin, pemetrexed, and pembrolizumab before the initiation of poziotinib. After a period of response to poziotinib, progression ensued. Repeat biopsy did not reveal on-target resistance mutations or alternative off-target aberrations (FoundationOne CDx). The patient received trastuzumab deruxtecan with rapid clinical and radiographic response that was maintained for 6 months before progressive disease developed. Patient 2, who had lung adenocarcinoma with an ERBB2 A775_G776insYVMA mutation, had not previously received treatment at the time of initiation of poziotinib. After a period of response, the patient had clinical and radiographic progression. Repeat biopsy did not reveal on-target resistance mutations or alternative off-target aberrations (FoundationOne CDx). The use of trastuzumab deruxtecan led to rapid clinical and radiographic improvement that is ongoing at the time of this report (>11 months). Patient 3, who had lung adenocarcinoma with an ERBB2 A775_G776insYVMA mutation, had received carboplatin, pemetrexed, and pembrolizumab, followed by trastuzumab emtansine (11 months, data not shown), followed by carboplatin and gemcitabine before the initiation of poziotinib. The best response to poziotinib was stable disease, and the best response to trastuzumab deruxtecan was stable disease for a 6-month period followed by eventual radiographic progression and death. Repeat tumor biopsy was not performed. Data on clinical, radiographic, and survival outcomes used to report these cases were obtained from an ongoing institutional review board–approved protocol at our institution.
See this image and copyright information in PMC

Comment in

Comment on

  • Trastuzumab Deruxtecan in HER2-Mutant Non-Small-Cell Lung Cancer.
    Li BT, Smit EF, Goto Y, Nakagawa K, Udagawa H, Mazières J, Nagasaka M, Bazhenova L, Saltos AN, Felip E, Pacheco JM, Pérol M, Paz-Ares L, Saxena K, Shiga R, Cheng Y, Acharyya S, Vitazka P, Shahidi J, Planchard D, Jänne PA; DESTINY-Lung01 Trial Investigators. Li BT, et al. N Engl J Med. 2022 Jan 20;386(3):241-251. doi: 10.1056/NEJMoa2112431. Epub 2021 Sep 18. N Engl J Med. 2022. PMID: 34534430 Free PMC article. Clinical Trial.

References

    1. Li BT, Smit EF, Goto Y, et al. Trastuzumab deruxtecan in HER2-mutant non–small-cell lung cancer. N Engl J Med 2022;386:241–51. - PMC - PubMed
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MeSH terms