Microtubule-targeting agents in the treatment of non-small cell lung cancer: insights on new combination strategies and investigational compounds

ABSTRACT

Introduction: The management of non-small cell lung cancer (NSCLC) has been substantially improved in the last few years; it has been revolutionized by a patient-tailored approach, especially in the oncogene addicted disease, and by novel combinations containing immune checkpoint inhibitors. However, chemotherapy still represents a mainstay that persists over the decades with limited novelties. Tubulin inhibitors belong to different sub-classes of drugs that share the capability to interfere with mitosis by a direct action on the microtubule system. Among them, taxanes and vinca alkaloids still have a prominent role in clinical practice.

Areas covered: This review summarizes the mechanisms of action, current role and future directions of microtubule targeting agents; we focus on investigational agents in phase I and II clinical trials.

Expert opinion: Chemotherapy maintains a pivotal role in the treatment of NSCLC. New generation agents that have the potential to overcome the mechanisms of resistance to the available drugs may provide new therapeutic opportunities. Predictive biomarkers derived from combination strategies and phase III studies are necessary going forward.

Trial registration: ClinicalTrials.gov identifier: NCT02309177.

Trial registration: ClinicalTrials.gov identifier: NCT02014337.

Trial registration: ClinicalTrials.gov identifier: NCT03102606.

Trial registration: EU Clinical Trials Register identifier: 021855-15.

Trial registration: ClinicalTrials.gov identifier: NCT01454934.

Trial registration: ClinicalTrials.gov identifier: NCT00651508.

Trial registration: ClinicalTrials.gov identifier: NCT02812667.

Trial registration: ClinicalTrials.gov identifier: NCT02846792.

Trial registration: ClinicalTrials.gov identifier: NCT02533674.

KEYWORDS:

• Non-small cell lung cancer
• tubulin inhibitors
• microtubule-targeting agents
• chemotherapy
• combinations
• phase I trial
• phase II trial

Article highlights

• Chemotherapy is still a mainstay in the approach to non-small cell lung cancer (NSCLC), despite the increasing importance of immune checkpoint inhibitors.

• Among different chemotherapies, microtubule-targeting agents (MTA), alone or in combination, represent the standard of care in different settings.

• New combination strategies involving MTA are being explored and are changing the treatment paradigm of advanced NSCLC.

• Investigational tubulin inhibitors that belong to a new generation of MTA have demonstrated encouraging results on clinical activity, particularly in phase I and II trials.

• Novel MTA represent an interesting class of drugs that need to be further investigated.

• Predictive biomarkers of response and strong evidence of efficacy necessary going forward.

• This box summarizes key points contained in the article.

Acknowledgments

Simona Coco is a PhD supported by grants from Italian Ministry of Health (Ricerca Corrente).

Declaration of interest

M Tagliamento received travel grants by Roche, Bristol-Myers Squib; C Genova received honoraria from AstraZeneca, Boehringer-Ingelheim, Bristol-MyersSquibb and Roche; G Rossi received honoraria as a medical writer from Amgen, Novartis, and Roche; E Rijavec received honoraria from Bristol-Myers Squibb, AstraZeneca, Boehringer-Ingelheim, Roche; F Grossi has consulting/advisory relationship with, and received honoraria from Eli Lilly and Company, Bristol-Myers Squibb, Merck Sharp & Dohme; P Fabre has consulting/advisory relationship with AstraZeneca and Roche. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This paper was not funded.