'Targeting' Improved Outcomes with Antibody-Drug Conjugates in Non-Small Cell Lung Cancer - An Updated Review

Sep 24, 2026

Uploaded by Oliver

Antibody-drug conjugates (ADCs) represent an emerging drug class designed to improve outcomes in specific cancers by delivering cytotoxic payloads to tumor cells expressing defined antigens. This review summarizes approved ADCs across hematologic and solid malignancies and highlights the clinical impact of trastuzumab deruxtecan in previously treated metastatic HER2-mutant NSCLC. It further surveys promising pipeline agents, including targets, efficacy, and safety in non-small cell lung cancer, and addresses toxicities, biomarkers, resistance mechanisms, and future clinical strategies.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages22

Reading Time55 min

AccessFree to download

Introduction

ADCs—Structure and Mechanism of Action

Structure

Antibody

Review `Targeting' Improved Outcomes with Antibody-Drug Conjugates in Non-Small Cell Lung Cancer—An Updated Review Saurav Verma 1,2, Daniel Breadner 1,2 and Jacques Raphael 1,2, * Citation: Verma, S.; Breadner, D.; Raphael, J. `Targeting' Improved Outcomes with Antibody-Drug Conjugates in Non-Small Cell Lung Cancer—An Updated Review. Curr. Oncol. 2023, 30, 4329–4350. [https://](https://)[ ](https://)[doi.org/10.3390/curroncol30040330](doi.org/10.3390/curroncol30040330) Received: 16 March 2023 Revised: 14 April 2023 Accepted: 18 April 2023 Published: 20 April 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Division of Medical Oncology, Department of Oncology, Schulich School of Medicine & Dentistry, Western University, London, ON N6A 5C1, Canada; [saurav.verma@lhsc.on.ca](saurav.verma@lhsc.on.ca) (S.V.); [daniel.breadner@lhsc.on.ca](daniel.breadner@lhsc.on.ca) (D.B.) 2 London Regional Cancer Program, London Health Sciences Centre, London, ON N6A 5W9, Canada * [Correspondence: jacques.raphael@lhsc.on.ca](Correspondence: jacques.raphael@lhsc.on.ca); Tel.: +1-(519)-685-8500 (ext. 53415) Abstract: Antibody-Drug conjugates (ADCs) are a relatively new class of drugs with a promise to improve the outcomes in speciﬁc cancers. By delivering the cytotoxic agent to tumor cells expressing speciﬁc antigens, ADCs achieve a better therapeutic index and more potency. ADCs have been approved for several hematological and solid malignancies, including breast, urothelial and gastric carcinoma. Recently, trastuzumab deruxtecan (TDXd) was the ﬁrst ADC approved for previously treated metastatic HER2-mutant non-small cell lung cancer (NSCLC) . Many promising ADCs are in the pipeline for clinical development in non-small cell lung cancer, including sacituzumab govitecan, patritumab deruxtecan, datopotamab deruxtecan and tusamitamab ravtansine. There is a hope that these drugs would cater to the unmet need of speciﬁc patient populations, including patients with currently untargetable mutations. We hope these drugs, e.g., TROP2 targeted ADCs, will also give more options for therapy in NSCLC to improve outcomes for patients. In this comprehensive review, we will be discussing the recent evidence including targets, efﬁcacy and the safety of newer ADC candidates in NSCLC. We will also brieﬂy discuss the speciﬁc toxicities, novel biomarkers, overcoming resistance mechanisms, challenges and the way forward, as these new ADCs and combinations ﬁnd away into the clinical practice. Keywords: Antibody-Drug conjugate; ADCs; non-small cell lung cancer (NSCLC) 1. Introduction Lung cancer is the second most common cancer worldwide and the leading cause of cancer-related deaths [1] . Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all new lung cancer cases and more than two-thirds are advanced/metastatic atthe initial diagnosis. With the continuing advancements in the genomic underpinnings of lung cancer, it is now at the helm of personalized therapy. The current systemic therapeutic arsenal of non-small cell lung cancer comprises chieﬂy immune checkpoint inhibitors (ICIs), targeted therapy and chemotherapy. Although these therapies have signiﬁcantly improved outcomes, there is hope for better options for speciﬁc populations lacking targetable driver mutations and those with the progression of disease on ﬁrst-line chemo-immunotherapy, which represent the largest unmet need in advanced/metastatic NSCLC with limited therapeutic options and poor prognosis. Antibody-Drug conjugates are a rapidly evolving class of biotherapeutics combining cytotoxic drugs and targeted antibodies. Combining these two moieties

FAQs

What are antibody-drug conjugates (ADCs) and why are they promising in non-small cell lung cancer?

ADCs combine a targeted antibody with a cytotoxic payload to deliver treatment selectively to cancer cells expressing the relevant antigen. This design aims to improve therapeutic index and potency while limiting systemic exposure.

Which ADC is highlighted as the first approved option for previously treated metastatic HER2-mutant NSCLC?

Trastuzumab deruxtecan (TDXd) is described as the first ADC approved for previously treated metastatic HER2-mutant non-small cell lung cancer, supported by evidence from a phase 2 study showing improved outcomes.

What topics does the review cover beyond targets and efficacy in NSCLC?

The review discusses safety, specific toxicities, novel biomarkers, and mechanisms to overcome resistance, along with challenges and future directions as ADCs and combinations move into clinical practice.

Sep 24, 2026

Uploaded by Oliver