Osimertinib after Chemoradiotherapy in Stage III EGFR-Mutated NSCLC
Osimertinib in adjuvant, now after chemotherapy and radiation, next… Neoadjuvant??? Trials are ongoing.
This is here till progression.
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, MARelated Articles
Sacituzumab Govitecan Versus Docetaxel for Previously Treated Advanced or Metastatic Non–Small Cell Lung Cancer: The Randomized, Open-Label Phase III EVOKE-01 Study
Failed? Numerical overall survival (OS) benefit for sacituzumab vs docetaxol, but not statistically significant. Better tolerated, also overall survival (OS) noticed more in patients who did not respond to antiPDL-1 therapy.
Phase II Efficacy and Safety of 80 mg Osimertinib in Patients With Leptomeningeal Metastases Associated With Epidermal Growth Factor Receptor Mutation–Positive Non–Small Cell Lung Cancer (BLOSSOM)
This is a very hard and depressing disease, but now with hope. EGFR-mutated NSCLS patients showed response to osimertinib in more than 50%, 15% complete response (CR), 15 months survival. This is promising, and maybe now we can study other TKIs in this mets.
Ivonescimab Plus Chemotherapy in Non–Small Cell Lung Cancer With EGFR Variant – A Randomized Clinical Trial
Bispecific (a bispecific antibody targeting programmed cell death 1 protein and vascular endothelial growth factor) and chemotherapy … and it worked … second line after EGFR therapy failure.
Amivantamab plus Lazertinib in Previously Untreated EGFR-Mutated Advanced NSCLC
Another possible option for first line NSCLC EGFR mutated (non-exon 20) is Osimertinib (osi). Osi and chemotherapy had less brain metastases. And with Amivantamab and Lazertinib (EGFR inhibitor), the combination had better PFS and OS (HR0.8). Higher toxicity though with 10% discontinuation vs 3% for Osimertinib. This is interim analysis, toxicity was EGFR related mostly.
