Durvalumab in combination with chemoradiotherapy for patients with unresectable stage III non-small-cell lung cancer : Results from the phase 1 CLOVER study
Kim, Dong-Wan (Seoul National University Hospital)
Chul Cho, Byoung (Yonsei University College of Medicine)
Pachipala, Krishna (Millenium Oncology)
Kim, Sang-We (University of Ulsan College of Medicine)
Wang, Chih-Liang (Chang-Gung Medical Foundation Linkou)
Chang, Gee-Chen (Taichung Veterans General Hospital)
Ahn, Myung-Ju (Sungkyunkwan University School of Medicine)
Alvarez, Rosa (Hospital General Universitario Gregorio Marañón. Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM))
Chiu, Chao-Hua (Taipei Veterans General Hospital)
Trigo, José Manuel (Hospital Universitario Virgen de la Victoria (Màlaga, Andalusia))
Estival, Anna (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Karam, Sana D. (Anschutz Medical Campus)
O'Brien, Cathy (AstraZeneca)
Gowda, Hema (AstraZeneca)
Jiang, Haiyi (AstraZeneca)
Bauman, Julie E. (University of Arizona Cancer Center)

Data:	2024
Resum:	Introduction: For patients with unresectable, stage III non-small-cell lung cancer (NSCLC), current standard of care is concurrent chemoradiotherapy (cCRT) followed by consolidation durvalumab. However, earlier initiation of durvalumab simultaneously with cCRT may increase antitumor activity relative to initiation after cCRT. The phase 1 CLOVER study (NCT03509012) evaluated durvalumab combined with cCRT in patients with advanced solid tumors; we report findings from the NSCLC cohort. Methods: CLOVER comprised a dose-limiting toxicity (DLT) assessment part, followed by an expansion part. In the NSCLC cohort, patients with previously untreated, unresectable, stage III NSCLC were enrolled in three treatment arms: durvalumab every 4 weeks (Q4W) + cisplatin + etoposide + radiotherapy (Arm 1); durvalumab Q4W + carboplatin + paclitaxel + radiotherapy (Arm 2); or durvalumab Q4W + carboplatin or cisplatin + pemetrexed + radiotherapy (non-squamous histology only; Arm 3). Patients received durvalumab until disease progression or unacceptable toxicity. The primary endpoint was safety and tolerability. Results: Sixty-four patients were enrolled: 21, 22, and 21 in Arms 1, 2, and 3, respectively. One patient in Arm 1 had DLT (grade 3 aspartate aminotransferase increase and grade 4 alanine aminotransferase increase); no DLTs were observed in Arms 2 or 3. Grade 3/4 adverse events occurred in 76. 6 % of patients overall; the most common were neutropenia (51. 6 %), leukopenia (20. 3 %), and anemia (17. 2 %). In a post-hoc analysis, 7. 8 % of patients had grade 3 pneumonitis/radiation pneumonitis (grouped term) events. Overall, the objective response rate was 60. 9 % (95 % confidence interval [CI], 47. 9-72. 9); median duration of response was 15. 8 months (95 % CI, 9. 0-not estimable [NE]). Median progression-free survival was 13. 4 months (95 % CI, 8. 8-20. 1) and median overall survival was not reached (95 % CI, 21. 9-NE). Conclusion: Durvalumab in combination with cCRT was well tolerated, with a manageable safety profile and showed encouraging antitumor activity in patients with unresectable, stage III NSCLC.
Nota:	This study was sponsored by AstraZeneca. The authors would like to thank the patients, their families and caregivers, and all investigators involved in this study. Medical writing support for the development of this manuscript, under the direction of the authors, was provided by Connor Keating of Ashfield MedComms (Manchester, UK), an Inizio company, and was funded by AstraZeneca. All patients provided written informed consent prior to participation in the study. The study was carried out in accordance with the principles set out in the Declaration of Helsinki and was consistent with the International Conference on Harmonisation guidelines on Good Clinical Practice, and any applicable local laws and requirements. The protocol and all subsequent amendments were approved by the relevant Ethics Committees/Independent Review Boards.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Durvalumab ; Unresectable ; Stage III NSCLC ; Concurrent chemoradiotherapy ; Phase 1 study
Publicat a:	Lung cancer, Vol. 190 (april 2024) , p. 107530, ISSN 1872-8332

DOI: 10.1016/j.lungcan.2024.107530

9 p, 886.9 KB

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