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Clinical Trial
. 2024 Nov;41(11):4125-4139.
doi: 10.1007/s12325-024-02975-x. Epub 2024 Sep 11.

Efficacy of Trastuzumab Deruxtecan in HER2-Expressing Solid Tumors by Enrollment HER2 IHC Status: Post Hoc Analysis of DESTINY-PanTumor02

Ana Oaknin  1 , Jung-Yun Lee  2 , Vicky Makker  3   4 , Do-Youn Oh  5   6   7 , Susana Banerjee  8   9 , Antonio González-Martín  10 , Kyung Hae Jung  11 , Iwona Ługowska  12 , Luis Manso  13 , Aránzazu Manzano  14 , Bohuslav Melichar  15 , Salvatore Siena  16   17 , Daniil Stroyakovskiy  18 , Anitra Fielding  19 , Soham Puvvada  19 , Ann Smith  20 , Funda Meric-Bernstam  21
Affiliations
Clinical Trial

Efficacy of Trastuzumab Deruxtecan in HER2-Expressing Solid Tumors by Enrollment HER2 IHC Status: Post Hoc Analysis of DESTINY-PanTumor02

Ana Oaknin et al. Adv Ther. 2024 Nov.

Abstract

Introduction: DESTINY-PanTumor02 (NCT04482309) evaluated the efficacy and safety of trastuzumab deruxtecan (T-DXd) in pretreated patients with human epidermal growth factor receptor 2 (HER2)-expressing [immunohistochemistry (IHC) 3+/2+] solid tumors across seven cohorts: endometrial, cervical, ovarian, bladder, biliary tract, pancreatic, and other. Subgroup analyses by HER2 status were previously reported by central HER2 IHC testing, determined at enrollment or confirmed retrospectively. Reflecting the testing methods available in clinical practice, most patients (n = 202; 75.7%) were enrolled based on local HER2 IHC testing. Here, we report outcomes by HER2 IHC status as determined by the local or central test results used for study enrollment.

Methods: This phase 2, open-label study evaluated T-DXd (5.4 mg/kg once every 3 weeks) for HER2-expressing (IHC 3+/2+ by local or central testing) locally advanced or metastatic disease after ≥ 1 systemic treatment or without alternative treatments. The primary endpoint was investigator-assessed confirmed objective response rate (ORR). Secondary endpoints included safety, duration of response (DOR), progression-free survival (PFS), and overall survival.

Results: In total, 111 (41.6%) and 151 (56.6%) patients were enrolled with IHC 3+ and IHC 2+ tumors, respectively. In patients with IHC 3+ tumors, investigator-assessed confirmed ORR was 51.4% [95% confidence interval (CI) 41.7, 61.0], and median DOR was 14.2 months (95% CI 10.3, 23.6). In patients with IHC 2+ tumors, investigator-assessed ORR was 26.5% (95% CI 19.6, 34.3), and median DOR was 9.8 months (95% CI 4.5, 12.6). Safety was consistent with the known profile of T-DXd.

Conclusion: In line with previously reported results, T-DXd demonstrated clinically meaningful benefit in patients with HER2-expressing tumors, with the greatest benefit in patients with IHC 3+ tumors. These data support the antitumor activity of T-DXd in HER2-expressing solid tumors, irrespective of whether patients are identified by local or central HER2 IHC testing.

Keywords: Advanced/metastatic solid tumors; HER2 testing; HER2-expressing; Trastuzumab deruxtecan.

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Conflict of interest statement

Ana Oaknin has received consulting fees from Agenus, AstraZeneca, Clovis Oncology, Corcept Therapeutics, Daiichi Sankyo, Debiopharm, Deciphera Pharmaceuticals, Eisai, Exelisis, Genmab, GSK, ImmunoGen, Itheos, MSD, Mersana Therapeutics, Myriad Genetics, Novocure, OncXerna Therapeutics, Pfizer, PharmaMar, Regeneron Pharmaceuticals, Roche, Shattuck Labs, Sutro Biopharma, and Zentalis Pharmaceuticals; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Asociación Colombiana de Ginecológos Oncólogos, AstraZeneca, European School of Oncology, GSK, Medscape, NSGO, PeerView, and PeerVoice; support for attending meetings and/or travel from AstraZeneca, PharmaMar, and Roche; participated on a Data Safety Monitoring Board or Advisory Board for Agenus, AstraZeneca, Clovis Oncology, Corcept Therapeutics, Daiichi Sankyo, Debiopharm, Deciphera Pharmaceuticals, Eisai, Exelisis, Genmab, GSK, ImmunoGen, Itheos, MSD, Mersana Therapeutics, Myriad Genetics, Novocure, OncXerna Therapeutics, Pfizer, PharmaMar, Regeneron Pharmaceuticals, Roche, Shattuck Labs, Sutro Biopharma, and Zentalis Pharmaceuticals; and held a leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid, for the European Society for Medical Oncology, as European Society for Medical Oncology Guidelines Gynecology Subject Editor, as European Society for Medical Oncology Gynecology Meeting Chair, as European Society for Medical Oncology Gynecology Faculty Member, for the Gynecologic Cancer Intergroup, and as Gynecologic Cancer Intergroup Cervical Cancer Committee Chair. Jung-Yun Lee has participated on a Data Safety Monitoring Board or Advisory Board for Eisai and GI Innovation Inc.; and has other financial or non-financial interests with Alkermes, AstraZeneca, BeiGene, BerGenBio, Cellid, Clovis Oncology, Eisai, GI Innovation, ImmunoGen, Janssen, Merck, Mersana Therapeutics, MSD, Novartis, OncoQuest Pharmaceuticals, ONO Pharmaceutical Co., Ltd., Roche, Seagen, Synthon, and Takeda Pharmaceuticals. Vicky Makker has received grants or contracts from AstraZeneca, Bristol-Myers Squibb, Clasi, Cullinan Therapeutics, Duality Biologics, Eisai, Faeth Therapeutics, Karyopharm Therapeutics, Merck, Takeda Pharmaceuticals, and Zymeworks; support for attending meetings and/or travel from Eisai, Karyopharm Therapeutics, and Merck; and has other financial or non-financial interests with Clovis, Cullinan Therapeutics, Duality Biologics, Eisai, Faeth Therapeutics, GSK, Immunocore, iTeos Therapeutics, Karyopharm Therapeutics, Lilly, Merck, Mereo BioPharma, MorphoSys, MSD, Novartis, Regeneron Pharmaceuticals, Sutro Biopharma, and Zymeworks. Do-Youn Oh has received grants or contracts from Array BioPharma, AstraZeneca, BeiGene, Eli Lilly and Company, HANDOK, MSD, Novartis, and Servier; and has participated on a Data Safety Monitoring Board or Advisory Board for Arcus Biosciences, ASLAN Pharmaceuticals, AstraZeneca, Basilea, Bayer, BeiGene, Bristol-Myers Squibb, Genentech/Roche, Halozyme, IQVIA, Merck, MSD, Novartis, Taiho Pharmaceutical Co., Ltd., Turning Point Therapeutics, Yuhan Corporation, and Zymeworks. Susanna Banerjee has received grants or contracts from AstraZeneca and GSK; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Amgen, AstraZeneca, Clovis Oncology, GSK, ImmunoGen, Medscape, Merck, Mersana Therapeutics, Novocure, Pfizer, Research to Practice, Roche, and Takeda Pharmaceuticals; support for attending meetings and/or travel from GSK and Verastem Oncology; participated on a Data Safety Monitoring Board or Advisory Board for AstraZeneca, Epsilogen, GSK, ImmunoGen, Merck, Mersana Therapeutics, Novartis, OncXerna Therapeutics, Seagen, Shattuck Labs, Regeneron Pharmaceuticals, and Verastem Oncology; held a leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, with the International Cancer Foundation; and has stock or stock options with Perci Health. Antonio González-Martín has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, Clovis Oncology, GSK, Novocure, MSD, Roche, Takeda Pharmaceuticals, and Zai Lab; support for attending meetings and/or travel from AstraZeneca, GSK, and MSD; participated on a Data Safety Monitoring Board or Advisory Board for Alkermes, Amgen, AstraZeneca, BioNTech, Clovis Oncology, Daiichi Sankyo, Eisai, Genmab, GSK, Hedera Dx, Illumina, ImmunoGen, Incyte Corporation, Kartos Therapeutics, MacroGenics, Mersana Therapeutics, MSD, Novartis, Novocure, Oncoinvent, PharmaMar, Regeneron Pharmaceuticals, Roche, Sutro Biopharma, SOTIO Biotech, and Tubulis; and has other financial or non-financial interests with GSK and Roche. Kyung Hae Jung has received consulting fees from AstraZeneca, BIXINK, Celgene, Daiichi Sankyo, Eisai, Everest Medicines, Gilead Sciences, MSD, Novartis, Pfizer, Roche, and Takeda Pharmaceuticals. Iwona Ługowska has received grants or contracts from Agenus and Roche; and has other financial or non-financial interests with Agenus, AstraZeneca, Amgen, Bristol-Myers Squibb, Celon Pharma SA, CliniNote, the European Society for Medical Oncology, Incyte, Janssen, Menarini, MSCI, MSD, the Organisation of European Cancer Institutes, Pfizer, Rhizen, Roche, Ryvu Therapeutics, and Sairopa. Luis Manso declares no conflicts of interest. Aránzazu Manzano has received grants or contracts from AstraZeneca; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, GSK, LEO Pharma, MSD, PharmaMar, and Sanofi; support for attending meetings and/or travel from AstraZeneca, GSK, and MSD; and participated on a Data Safety Monitoring Board or Advisory Board for Boehringer Ingelheim, GSK, and PharmaMar. Bohuslav Melichar has received consulting fees from AstraZeneca, Amgen, Bristol-Myers Squibb, Lilly, Merck, MSD, Novartis, Pfizer, Roche, and Servier; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, Amgen, Bristol-Myers Squibb, EMD Serono, Lilly, Merck, MSD, Novartis, Pfizer, Roche, and Servier; support for attending meetings and/or travel from AstraZeneca, Bristol-Myers Squibb, Merck, and MSD; and has participated on a Data Safety Monitoring Board or Advisory Board for AstraZeneca, Bristol-Myers Squibb, Lilly, Merck, MSD, Novartis, Pfizer, and Roche. Salvatore Siena has participated on a Data Safety Monitoring Board or Advisory Board for Agenus, AstraZeneca, Bristol-Myers Squibb, Checkmab, Daiichi Sankyo, GSK, MSD, Novartis, Seagen, and T-ONE Therapeutics. Daniil Stroyakovskiy declares no conflicts of interest. Anitra Fielding holds stock or stock options with AstraZeneca and discloses other financial or non-financial interests with AstraZeneca (employment). Soham Puvvada holds stock or stock options with AstraZeneca and discloses other financial or non-financial interests with AstraZeneca (employment). Ann Smith holds stock or stock options with AstraZeneca and discloses other financial or non-financial interests with AstraZeneca (employment). Funda Meric-Bernstam has received grants or contracts from Aileron Therapeutics, AstraZeneca, Bayer, Calithera Biosciences, Curis, Inc., CytomX Therapeutics, Daiichi Sankyo, Debiopharm, eFFECTOR Therapeutics, Genentech Inc., Guardant Health, KLUS Pharma, Novartis, Puma Biotechnology, Takeda Pharmaceuticals, and Taiho Pharmaceutical Co., Ltd.; consulting fees from AbbVie, AstraZeneca, BD, Calibr-Skaggs at Scripps Research, Daiichi Sankyo, EcoR1 Capital, eFFECTOR Therapeutics, Exelixis, GT Apeiron, Incyte, Infinity Pharmaceuticals, Jazz Pharmaceuticals, LegoChem Biosciences, Lengo Therapeutics, Menarini, Molecular Templates, Protai, Roche, Tallac Therapeutics, and Zymeworks; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from DAVA Oncology; received support for attending meetings and/or travel from the Cholangiocarcinoma Foundation, the European Organisation for Research and Treatment of Cancer, the European Society for Medical Oncology, and DAVA Oncology; and participated on a Data Safety Monitoring Board or Advisory Board for Black Diamond Therapeutics, Biovica International AB, Eisai, FogPharma, Harbinger Health, Karyopharm Therapeutics, Loxo Oncology, Mersana Therapeutics, OnCusp Therapeutics, Sanofi, Seagen, Theratechnologies, and Zentalis Pharmaceuticals.

Figures

Fig. 1
Fig. 1
ORR and DOR according to tumor type and HER2 IHC status by the local or central test result used for study enrollment by a investigator assessment and b ICR in patients with IHC 3+ and IHC 2+ tumors. BTC biliary tract cancer, CI confidence interval, DOR duration of response, HER2 human epidermal growth factor receptor 2, ICR independent central review, IHC immunohistochemistry, NE not estimable, ORR objective response rate
See this image and copyright information in PMC

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