Trastuzumab Deruxtecan in Anti–Human Epidermal Growth Factor Receptor 2 Treatment–Naive Patients With Human Epidermal Growth Factor Receptor 2–Low Gastric or Gastroesophageal Junction Adenocarcinoma: Exploratory Cohort Results in a Phase II Trial

Author(s): Kensei Yamaguchi, MD¹;Yung-Jue Bang, MD, PhD²;Satoru Iwasa, MD³;Naotoshi Sugimoto, MD⁴;Min-Hee Ryu, MD, PhD⁵;Daisuke Sakai, MD⁶;Hyun Cheol Chung, MD, PhD⁷;Hisato Kawakami, MD, PhD⁸;Hiroshi Yabusaki, MD⁹;Jeeyun Lee, MD¹⁰;Tatsu Shimoyama, MD¹¹;Keun-Wook Lee, MD, PhD¹²;Kaku Saito, MSc, MBA¹³;Yoshinori Kawaguchi, MSc, MBA¹³;Takahiro Kamio, MD¹³;Akihito Kojima, MSc¹⁴;Masahiro Sugihara, PhD¹⁴;and Kohei Shitara, MD¹⁵

Source: DOI: 10.1200/JCO.22.00575 Journal of Clinical Oncology

Dr. Anjan Patel's Thoughts

Her2-low is here to stay. Expect further studies on Enhertu and Trodelvy for gastroesophageal Her-2 low patients. Response rates were modest however, so temper expectations as single agent therapy. I look forward to trials on future combination therapy.

PURPOSE

To investigate efficacy and safety of trastuzumab deruxtecan (T-DXd) in human epidermal growth factor receptor 2 (HER2)–low gastric or gastroesophageal junction (GEJ) adenocarcinoma.

METHODS

Patients with locally advanced or metastatic HER2-low (cohort 1, immunohistochemistry 2+/in situ hybridization–negative; cohort 2, immunohistochemistry 1+) gastric/GEJ adenocarcinoma treated with at least two prior regimens, including fluoropyrimidine and platinum, but anti-HER2 therapy naive, received T-DXd 6.4 mg/kg intravenously once every 3 weeks. The primary end point was confirmed objective response rate by independent central review.

RESULTS

Among 21 patients enrolled in cohort 1 and 24 enrolled in cohort 2, 19 and 21 patients, respectively, had central HER2 confirmation, received T-DXd, and had measurable tumors at baseline. The confirmed objective response rate was 26.3% (95% CI, 9.1 to 51.2) from five partial responses in cohort 1 and 9.5% (95% CI, 1.2 to 30.4) from two partial responses in cohort 2. Thirteen patients (68.4%) in cohort 1 and 12 (60.0%) in cohort 2 experienced reduced tumor size. The median overall survival was 7.8 months (95% CI, 4.7 to nonevaluable) in cohort 1 and 8.5 months (95% CI, 4.3 to 10.9) in cohort 2; the median progression-free survival was 4.4 months (95% CI, 2.7 to 7.1) and 2.8 months (95% CI, 1.5 to 4.3), respectively. The most common grade ≥ 3 treatment-emergent adverse events in cohorts 1 and 2 were anemia (30.0% and 29.2%), decreased neutrophil count (25.0% and 29.2%), and decreased appetite (20.0% and 20.8%). Drug-related interstitial lung disease/pneumonitis occurred in one patient in each cohort (grade 1 or 2). No drug-related deaths occurred.

CONCLUSION

This study provides preliminary evidence that T-DXd has clinical activity in patients with heavily pretreated HER2-low gastric/GEJ adenocarcinoma.

Author Affiliations

¹Gastroenterological Chemotherapy Department, The Cancer Institute Hospital of JFCR, Tokyo, Japan;²Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea;³Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan;⁴Department of Medical Oncology, Osaka International Cancer Institute, Osaka, Japan;⁵Department of Oncology, Asan Medical Center, Seoul, South Korea;⁶Department of Frontier Science for Cancer and Chemotherapy, Osaka University Hospital, Osaka, Japan;⁷Department of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea;⁸Department of Medical Oncology, Kindai University Hospital, Osaka, Japan;⁹Department of Medical Oncology, Niigata Cancer Center Hospital, Niigata, Japan;¹⁰Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, South Korea;¹¹Department of Medical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan;¹²Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea;¹³Daiichi Sankyo, Inc, Basking Ridge, NJ;¹⁴Daiichi Sankyo, Tokyo, Japan;¹⁵Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan

Perioperative Chemotherapy or Preoperative Chemoradiotherapy in Esophageal Cancer

Full publication of the ESOPEC trial which was presented at ASCO-2024. Essentially perioperative FLOT beat preoperative carbo/taxol/XRT. One call out is that this study began before the era of using postoperative IO therapy for those with residual disease at the time of esophagectomy after neoadjuvant chemoradiation. Also, I would suggest that for bulky or node+ tumors, it may be worthwhile to consider a TNT-type approach as only ~50% of patients complete the four postoperative cycles of FLOT.

Trastuzumab Deruxtecan in Anti–Human Epidermal Growth Factor Receptor 2 Treatment–Naive Patients With Human Epidermal Growth Factor Receptor 2–Low Gastric or Gastroesophageal Junction Adenocarcinoma: Exploratory Cohort Results in a Phase II Trial

Dr. Anjan Patel's Thoughts

PURPOSE

METHODS

RESULTS

CONCLUSION

Author Affiliations

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Perioperative Chemotherapy or Preoperative Chemoradiotherapy in Esophageal Cancer

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