Trastuzumab Deruxtecan in Patients With HER2-Mutant Metastatic Non–Small-Cell Lung Cancer: Primary Results From the Randomized, Phase II DESTINY-Lung02 Trial

Author(s): Koichi Goto, MD, PhD¹; Yasushi Goto, MD, PhD²; Toshio Kubo, MD, PhD³; Kiichiro Ninomiya, MD, PhD⁴; Sang-We Kim, MD, PhD⁵; David Planchard, MD, PhD⁶; Myung-Ju Ahn, MD, PhD⁷; Egbert F. Smit, MD, PhD⁸; Adrianus Johannes de Langen, MD, PhD⁹; Maurice Pérol, MD¹⁰; Elvire Pons-Tostivint, MD, PhD¹¹; Silvia Novello, MD, PhD¹²; Hidetoshi Hayashi, MD, PhD¹³; Junichi Shimizu, MD, PhD¹⁴; Dong-Wan Kim, MD, PhD¹⁵; Chih-Hsi Kuo, MD, PhD¹⁶; James Chih-Hsin Yang, MD, PhD¹⁷; Kaline Pereira, MD, PhD¹⁸; Fu-Chih Cheng, PhD¹⁸; Ayumi Taguchi, PharmD¹⁹; Yingkai Cheng, MD, PhD¹⁸; Wenqin Feng, PhD¹⁸; Zenta Tsuchihashi, PhD¹⁸; and Pasi A. Jänne, MD, PhD²⁰

Source: DOI: 10.1200/JCO.23.01361 Journal of Clinical Oncology 41, no. 31 (November 01, 2023) 4852-4863.

Dr. Anjan Patel's Thoughts

Preliminary results of DESTINY-Lung02 show strong efficacy with trastuzumab deruxtecan (T-DXd). Overall response rate (ORR) was about 50%, with duration of response of 16.8 months. This is now FDA-approved and is an available therapy for patients with ERBB2 mutations after 1st line platinum-based chemo +/- immunotherapy. This is preferred over traditional trastuzumab or afatinib. Interestingly, some responses were seen in the ERBB2-negative patients who had over-expression by IHC. Please continue to sequence your patients and enroll in targeted therapy trials.

PURPOSE

Trastuzumab deruxtecan (T-DXd) 5.4 and 6.4 mg/kg showed robust antitumor activity in multiple cancer indications; however, T-DXd 5.4 mg/kg has not been evaluated in patients with previously treated human epidermal growth factor receptor 2–mutant (HER2m; defined as single-nucleotide variants and exon 20 insertions) metastatic non–small-cell lung cancer (mNSCLC).

METHODS

DESTINY-Lung02, a blinded, multicenter, phase II study, investigated T-DXd 5.4 mg/kg once every 3 weeks for the first time in previously treated (platinum-containing therapy) patients with HER2m mNSCLC and further assessed T-DXd 6.4 mg/kg once every 3 weeks in this population. The primary end point was confirmed objective response rate (ORR) per RECIST v1.1 by blinded independent central review.

RESULTS

One hundred fifty-two patients were randomly assigned 2:1 to T-DXd 5.4 or 6.4 mg/kg once every 3 weeks. As of December 23, 2022, the median duration of follow-up was 11.5 months (range, 1.1-20.6) with 5.4 mg/kg and 11.8 months (range, 0.6-21.0) with 6.4 mg/kg. Confirmed ORR was 49.0% (95% CI, 39.0 to 59.1) and 56.0% (95% CI, 41.3 to 70.0) and median duration of response was 16.8 months (95% CI, 6.4 to not estimable [NE]) and NE (95% CI, 8.3 to NE) with 5.4 and 6.4 mg/kg, respectively. Median treatment duration was 7.7 months (range, 0.7-20.8) with 5.4 mg/kg and 8.3 months (range, 0.7-20.3) with 6.4 mg/kg. Grade ≥ 3 drug-related treatment-emergent adverse events occurred in 39 of 101 (38.6%) and 29 of 50 (58.0%) patients with 5.4 and 6.4 mg/kg, respectively. 13 of 101 (12.9%) and 14 of 50 (28.0%) patients had adjudicated drug-related interstitial lung disease (2.0% grade ≥ 3 in each arm) with 5.4 and 6.4 mg/kg, respectively.

CONCLUSION

T-DXd demonstrated clinically meaningful responses at both doses. Safety profile was acceptable and generally manageable, favoring T-DXd 5.4 mg/kg.

Author Affiliations

¹National Cancer Center Hospital East, Kashiwa, Japan; ²National Cancer Center Hospital, Tokyo, Japan; ³Center for Clinical Oncology, Okayama University Hospital, Okayama, Japan; ⁴Okayama University Hospital, Okayama, Japan; ⁵Asan Medical Center, Seoul, Republic of Korea; ⁶Gustave Roussy, Department of Medical Oncology, Thoracic Group, Villejuif, France; ⁷Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; ⁸Leiden University Medical Center, Leiden, the Netherlands; ⁹Netherlands Cancer Institute, Amsterdam, the Netherlands; ¹⁰Léon Bérard Center, Lyon, France; ¹¹Centre Hospitalier Universitaire Nantes, Nantes University, Nantes, France; ¹²Department of Oncology, Azienda Ospedaliero-Universitaria San Luigi Gonzaga, Orbassano, University of Turin, Turin, Italy; ¹³Kindai University Hospital, Osaka, Japan; ¹⁴Aichi Cancer Center Hospital, Aichi, Japan; ¹⁵Seoul National University College of Medicine and Seoul National University Hospital, Seoul, South Korea; ¹⁶Chang Gung Memorial Hospital, Chang Gung University, Taipei, Taiwan; ¹⁷National Taiwan University Hospital and National Taiwan University Cancer Center, Taipei, Taiwan; ¹⁸Daiichi Sankyo Inc, Basking Ridge, NJ; ¹⁹Daiichi Sankyo, Tokyo, Japan; ²⁰Dana-Farber Cancer Institute, Boston, MA

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