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The Challenges Faced in Developing Novel Drug Radiation Combinations in Non-small Cell Lung Cancer

Harrow, S., Hanna, G.G., Faivre-Finn, C., McDonald, F., Chalmers, A.J.

Journal of Clinical Oncology - Volume 28, Issue 11, Pages 720–725

Approaching a Consensus Towards Drug‐Radiotherapy Combination in Non-small Cell Lung Cancer

Radiotherapy is a gold standard treatment for non-small cell lung cancer (NSCLC) but therecurrence rates could be high. One of the approaches to improve the efficacy of radiotherapy isto co-administer systemic drugs. This combination of drug and radiation therapy could be ofpotential benefit in patients with localized and curable disease.

Some of the important issues to consider when administering combination therapy of radiation andsystemic drugs is tumour biology and resistance to radiation. Because of the characteristic tumourheterogeneity in NSCLC influencing the response to therapy, it is important to design innovativetrials appropriately assessing success of the combination treatment.

In order to address the opportunities and challenges in combination treatment with novel systemicdrugs and radiation therapy in NSCLC, a two-day workshop was organized in 2016 by the NationalCancer Research Institute (NCRI), UK with an aim to develop and implement high-quality clinicaltrials.
In addition to agreeing to the optimal dose of 2 Gy in radiotherapy when combining with noveldrugs, the consensus also identified two specific interventions and patient populations for inclusionin future clinical trials. One of the interventions was the combination of curative intentradiotherapy with DNA damage response (DDR) inhibitors in patients with stage III NSCLC. Theother was combination of radiotherapy with immunomodulating agents in patients with stage IVNSCLC. They further agreed to analyze toxicity measures as primary endpoints in phase I trials ofcombined therapy (novel agents along with radiotherapy).

The consensus concluded with a resolution for initiating efforts towards realising the findings ofthe workshop by building the necessary infrastructure for implementing the proposed studies.

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