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Current Oncology
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Hype or Hope—Combination Therapies for Lung Cancer
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Hype or Hope—Combination Therapies for Lung Cancer

A special issue of Current Oncology (ISSN 1718-7729). This special issue belongs to the section "Thoracic Oncology".

Deadline for manuscript submissions: 31 May 2025 | Viewed by 4740

Special Issue Editor

Dr. Daniel Breadner

E-Mail Website
Guest Editor
London Regional Cancer Program, Division of Medical Oncology, London Health Science Center, London, ON, Canada
Interests: NSCLC; chemo-immunotherapy; immunotherapy; chemoradiation; SCLC; combination therapies; duo-immunotherapy; targeted therapy

Special Issue Information

Dear Colleagues,

This issue looks to explore the progress and future potential of combination therapies in lung cancer. From chemo-immunotherapy to combined immunotherapies to combining different modalities of therapy it will seek to explore how these have changed and are seeking change the treatment of lung cancer. In this Special Issue, original research articles and reviews about combination therapies in patients with lung cancer are welcome.

I look forward to receiving your contributions. 

Dr. Daniel Breadner
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Current Oncology is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • NSCLC
  • chemo-immunotherapy
  • immunotherapy
  • chemoradiation
  • SCLC
  • combination therapies
  • duo-immunotherapy
  • targeted therapy

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Published Papers (4 papers)

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Research

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13 pages, 660 KiB  
Article
Time to Next Treatment Following Sub-Ablative Progression Directed Radiation Therapy for Oligoprogressive Non-Small-Cell Lung Cancer
by Riccardo Ray Colciago, Chiara Chissotti, Federica Ferrario, Maria Belmonte, Giorgio Purrello, Valeria Faccenda, Denis Panizza, Stefania Canova, Gaia Passarella, Diego Luigi Cortinovis and Stefano Arcangeli
Curr. Oncol. 2024, 31(11), 6840-6852; https://doi.org/10.3390/curroncol31110505 - 2 Nov 2024
Viewed by 1464
Abstract
We aimed to evaluate whether progression-directed radiation therapy (PDRT) can prolong the initiation of a subsequent systemic therapy regimen in a cohort of patients with oligoprogressive NSCLC. A retrospective analysis was conducted on NSCLC patients who underwent PDRT for extracranial oligoprogressive NSCLC, defined [...] Read more.
We aimed to evaluate whether progression-directed radiation therapy (PDRT) can prolong the initiation of a subsequent systemic therapy regimen in a cohort of patients with oligoprogressive NSCLC. A retrospective analysis was conducted on NSCLC patients who underwent PDRT for extracranial oligoprogressive NSCLC, defined as limited (up to five) progressing lesions following initial complete, partial, or stable response to systemic therapy according to REC1ST 1.1 and/or PERCIST 1.0 criteria. Cox proportional hazard regressions were performed to identify factors influencing time to next treatment (TTNT), which was considered the primary endpoint. Forty patients were analyzed. First, second, and ≥3 lines of systemic therapy were administered in 22 (58.2%), 14 (27.2%), and 4 (14.6%) cases, respectively. The median total dose was 36 Gy (range: 12–60) in five fractions (1–10), with a median biological effective dose for tumor control (BED10) of 52 Gy (26.4–151.2). After a median follow-up of 11 months (2–50), PDRT delayed further systemic therapy in 32 (80.0%) treatments. Median TTNT was not reached at 8 months (1–47) with a one-year Kaplan–Meier estimate of 81.4% (95% CI: 75.0% to 87.8%). No >grade 3 adverse event was observed. On multivariate analysis, patients with ≥3 lines of systemic therapy and/or with larger CTV volumes did not benefit from PDRT. Despite the use of sub-ablative doses, our findings show that PDRT represents an effective, safe, and viable option for oligoprogressive NSCLC. Patients irradiated early during their systemic treatment course, with a low volume of disease and nonmetastatic oligoprogression, could derive substantial benefits from PDRT. Full article
(This article belongs to the Special Issue Hype or Hope—Combination Therapies for Lung Cancer)
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12 pages, 1745 KiB  
Article
Current Radiotherapy Management of Extensive-Stage Small-Cell Lung Cancer in the Immunotherapy Era: An Italian National Survey on Behalf of the Italian Association of Radiotherapy and Clinical Oncology (AIRO)
by Alessio Bruni, Vieri Scotti, Maria Alessia Zerella, Federica Bertolini, Jessica Imbrescia, Emanuela Olmetto, Chiara Bennati, Francesco Cuccia, Marianna Miele, Niccolò Giaj-Levra, Marcello Tiseo, Patrizia Ciammella, Stefano Vagge, Marco Galaverni, Antonio Pontoriero, Serena Badellino, Ruggero Spoto, Emanuele Alì and Paolo Borghetti
Curr. Oncol. 2024, 31(11), 6791-6802; https://doi.org/10.3390/curroncol31110501 - 1 Nov 2024
Cited by 1 | Viewed by 1306
Abstract
Background: Extensive-stage small-cell lung cancer (ES-SCLC) treatment has recently been revolutionized by the advent of immune checkpoint inhibitors. This survey was conducted to evaluate the current pattern of care among Italian clinicians, in particular about the integration with radiation therapy (RT). Methods: In [...] Read more.
Background: Extensive-stage small-cell lung cancer (ES-SCLC) treatment has recently been revolutionized by the advent of immune checkpoint inhibitors. This survey was conducted to evaluate the current pattern of care among Italian clinicians, in particular about the integration with radiation therapy (RT). Methods: In June 2023, 225 Italian cancer care professionals were invited to complete a 21-question web-based survey about ES-SCLC management through personal contacts and the Italian Association for Radiotherapy and Clinical Oncology (AIRO) network. Results: We received 90 responses; the majority were radiation oncologists (89%) with more than 10 years of experience (51%). The preferred management of ES-SCLC in patients with a good performance status was concomitant chemo-immunotherapy (84%). Almost all respondents recommended prophylactic cranial irradiation (PCI) (85%), taking into account age and thoracic response; PCI was performed mainly between the end of chemotherapy and before starting immunotherapy (37%), with a three-dimensional conformal technique (46%). Furthermore, 83% of respondents choose to deliver thoracic RT in the case of both an intrathoracic and extrathoracic response, with an RT schedule of 30 Gy/10 fractions. Stereotactic RT is increasingly being used in oligoprogressions. Conclusions: Our analysis showed the variability of real-world management of ES-SCLC. Future clinical trials and developments are needed to improve the multidisciplinary treatment of these patients. Full article
(This article belongs to the Special Issue Hype or Hope—Combination Therapies for Lung Cancer)
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Review

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15 pages, 1197 KiB  
Review
ADCs and TCE in SCLC Therapy: The Beginning of a New Era?
by Paola Muscolino, Fausto Omero, Desirèe Speranza, Carla Infurna, Silvana Parisi, Vincenzo Cianci, Massimiliano Berretta, Alessandro Russo and Mariacarmela Santarpia
Curr. Oncol. 2025, 32(5), 261; https://doi.org/10.3390/curroncol32050261 - 30 Apr 2025
Viewed by 212
Abstract
The therapeutic landscape for small cell lung cancer (SCLC) has remained stationary for decades, with chemotherapy representing the sole treatment strategy, with a modest survival benefit. The addition of immune checkpoint inhibitors (ICIs) to standard first-line chemotherapy for SCLC was a considerable milestone. [...] Read more.
The therapeutic landscape for small cell lung cancer (SCLC) has remained stationary for decades, with chemotherapy representing the sole treatment strategy, with a modest survival benefit. The addition of immune checkpoint inhibitors (ICIs) to standard first-line chemotherapy for SCLC was a considerable milestone. However, despite high overall response rates, this strategy failed to deliver long-term benefits for most patients, who continue to face a poor prognosis. Over the last few years, a deeper knowledge of the molecular biology of SCLC and the impressive advancements in drug development, have led to the generation of novel classes of systemic therapies that promise to revolutionize the current therapeutic scenario. Among the various therapeutic approaches in development, T-cell Engagers (TCE) and antibody-drug conjugates (ADCs) stand out due to their unique structural characteristics and mechanisms of action. These therapies represent a paradigm shift from traditional monoclonal antibody (mAb) and chemotherapy regimens, allowing direct engagement of multiple targets associated with tumor progression. In this review, we provide an overview of current drug development in SCLC, specifically focusing on these new agents, summarizing available evidence, and tracking future directions. Full article
(This article belongs to the Special Issue Hype or Hope—Combination Therapies for Lung Cancer)
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26 pages, 1932 KiB  
Review
Unveiling the Synergistic Potential: Bispecific Antibodies in Conjunction with Chemotherapy for Advanced Non-Small-Cell Lung Cancer Treatment
by Saqib Raza Khan and Daniel Breadner
Curr. Oncol. 2025, 32(4), 206; https://doi.org/10.3390/curroncol32040206 - 31 Mar 2025
Viewed by 1038
Abstract
Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small-cell lung cancer (NSCLC) accounting for the majority of the cases. Despite advancements in targeted therapies and immunotherapies, many patients still rely on chemotherapy, highlighting the need for innovative treatment strategies. Bispecific [...] Read more.
Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small-cell lung cancer (NSCLC) accounting for the majority of the cases. Despite advancements in targeted therapies and immunotherapies, many patients still rely on chemotherapy, highlighting the need for innovative treatment strategies. Bispecific antibodies (bsAbs), which feature two distinct binding sites capable of targeting different antigens, have emerged as a promising therapeutic approach, particularly in combination with chemotherapy. This review explores the scientific evolution and clinical application of bsAbs in NSCLC, focusing on their synergistic potential with chemotherapy. BsAbs, such as amivantamab, which targets EGFR and MET, have demonstrated significant efficacy in clinical trials, particularly in patients with EGFR mutations. The combination of bsAbs with chemotherapy enhances immune-mediated tumor destruction by modulating the tumor microenvironment and overcoming resistance mechanisms. Recent clinical trials have shown improved progression-free survival and overall survival when bsAbs such as amivantamab are combined with chemotherapy, underscoring their potential to transform NSCLC treatment. Many other clinical trials are underway that are evaluating newer bsAbs, such as ivonescimab, which targets PD1 and VEGF. This review also discusses ongoing clinical trials investigating various bsAbs targeting EGFR, PD-1, PD-L1, HER2, and other pathways, highlighting the future directions of bsAb-based therapies. As the field evolves, bsAbs are poised to become a cornerstone of multimodal NSCLC treatment, offering more effective and personalized therapeutic options for patients with advanced disease. Full article
(This article belongs to the Special Issue Hype or Hope—Combination Therapies for Lung Cancer)
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