Durvalumab consolidation in patients with unresectable stage III non-small cell lung cancer with driver genomic alterations

Riudavets, Mariona; Auclin, Édouard; Mosteiro, Miguel A.; Dempsey, Naomi; Majem, Margarita; Lobefaro, Riccardo; López-Castro, Rafael; Bosch-Barrera, Joaquim; Pilotto, Sara; Escalera, E.; Tagliamento, Marco; Mosquera, Joaquín; Zalcman, Gérard; Nana, Frank Aboubakar; Ponce, Santiago; Maso, Alessandro Dal; Spotti, Martina; Mielgo-Rubio, Xabier; Mussat, Elodie; Reyes, Roxana; Benítez, José-Carlos; Lupinacci, L.; Duchemann, Boris; Giglio, Andrea De; Blaquier, Juan Bautista; Audigier-Valette, Clarisse; Scheffler, Matthias; Nadal, Ernest; Lopes, Gilberto; Signorelli, Diego; García‐Campelo, Rosario; Menis, Jessica; Bluthgen, Virginia; Campayo, Marc; Recondo, Gonzálo; Besse, Benjamin; Planchard, David; Mezquita, Laura

doi:10.1016/j.ejca.2022.02.014

Cited by 38 publications

(31 citation statements)

References 14 publications

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“…Several retrospective studies have also demonstrated smaller benefits of durvalumab consolidation in EGFR positive NSCLC compared to wild‐type patients following chemoradiation 30,31 . Recently, a multicenter retrospective analysis involving 323 stage III NSCLC patients across Europe and America reported limited activity of consolidation durvalumab in those harboring EGFR mutation, BRAF mutation and ALK rearrangement, but not for those harboring KRAS mutation 32 . In our study, both EGFR ‐mutation positive and WT patients had longer PFS and OS with durvalumab consolidation compared to CCRT alone.…”

Section: Discussionmentioning

confidence: 99%

Real‐world experience of consolidation durvalumab after concurrent chemoradiotherapy in stage III non‐small cell lung cancer

et al. 2022

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Background: Durvalumab consolidation is associated with improved survival following concurrent chemoradiotherapy (CCRT) in patients with stage III non-small cell lung cancer (NSCLC). Given the heterogeneity of stage III NSCLC patients, in this study we evaluated the efficacy and safety of durvalumab in the real-world setting. Method: Unresectable stage III NSCLC patients were retrospectively studied: one cohort received CCRT, another had CCRT-durvalumab. Primary endpoints were progression-free survival (PFS) and overall survival (OS), secondary endpoints were relapse rate and safety. In CCRT-durvalumab cohort, association between blood markers with survival and pneumonitis risk were analyzed. Results: A total of 84 patients were enrolled: 45 received CCRT, and 39 received CCRT-durvalumab. Median PFS was 17.5 months for CCRT-durvalumab and 8.9 months for CCRT-alone (HR 0.47, p = 0.038). Median OS was not-reached for CCRT-durvalumab and 22.3 months for CCRT-alone (HR 0.35, p = 0.024). Both EGFR-positive and wild-type (WT) patients had numerically improved PFS with durvalumab consolidation compared to CCRT-alone, 17.5 versus 10.9 months and 11.8 versus 6.63 months, respectively (interaction p-value = 0.608). Grade 2+ pneumonitis was detected in 25% of patients in the durvalumab cohort. Most pneumonitis occurred at 3.5 weeks after durvalumab initiation. Baseline neutrophil-to-lymphocyte ratio (NLR) ≥ 3 and ≥5 were associated with shorter PFS with durvalumab. Week 6 platelet-lymphocyte-ratio ≥ 180 was associated with a lower risk of pneumonitis. Conclusion:In this real-world study, durvalumab consolidation post CCRT was associated with a statistically significant improvement in PFS and OS. Effect of durvalumab on PFS was not modified by EGFR status. Active surveillance for pneumonitis is crucial. Baseline NLR may help to predict the benefit of treatment with durvalumab.

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Section: Discussionmentioning

confidence: 99%

Real‐world experience of consolidation durvalumab after concurrent chemoradiotherapy in stage III non‐small cell lung cancer

et al. 2022

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“…5 A multicentre retrospective analysis (n ¼ 323, driver mutation cohort n ¼ 17) showed a median PFSdcounted from the start of durvalumabdof 9 months in patients with EGFR-mutated NSCLC and w8 months in patients with either BRAF V600E mutation or ALK alterations. 80,81 A multiinstitutional retrospective analysis (n ¼ 37) showed no statistically significant benefit in patients with EGFR mutation treated with durvalumab after CCRT compared with placebo. In addition, 40% of patients suspended durvalumab due to severe irAEs.…”

Section: Immunotherapy In Patients With Stage III Nsclc Harboring Dri...mentioning

confidence: 99%

Immunotherapy in unresectable stage III non-small-cell lung cancer: state of the art and novel therapeutic approaches

et al. 2022

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“…More recently, a multicenter retrospective study showed limited activity in patients with stage III unresectable NSCLC with driver genomic alterations treated with durvalumab (PD-L1 inhibitor) after chemoradiotherapy, especially in the ALK rearrangement subgroup. The median progression-free survival (PFS) was not reached (11.3-NR) in the KRAS-mutation vs. 8.1 month in the EGFR-mutation vs. 7.8 month in the BRAF-mutation/ALK rearrangement (P = 0.02) ( 57 ). Therefore, current research on ALK-positive patients has mainly focused on ALK inhibitor resistance ( 58 ).…”

Section: Current Landscape Of Immunotherapy Of Alk-altered Tumorsmentioning

confidence: 99%

Anaplastic lymphoma kinase-special immunity and immunotherapy

Guo

Guo²,

Zhang³

et al. 2022

Front. Immunol.

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Alterations in the anaplastic lymphoma kinase (ALK) gene play a key role in the development of various human tumors, and targeted therapy has transformed the treatment paradigm for these oncogene-driven tumors. However, primary or acquired resistance remains a challenge. ALK gene variants (such as gene rearrangements and mutations) also play a key role in the tumor immune microenvironment. Immunotherapy targeting the ALK gene has potential clinical applications. Here, we review the results of recent studies on the immunological relevance of ALK-altered tumors, which provides important insights into the development of tumor immunotherapies targeting this large class of tumors.

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Durvalumab consolidation in patients with unresectable stage III non-small cell lung cancer with driver genomic alterations

Cited by 38 publications

References 14 publications

Real‐world experience of consolidation durvalumab after concurrent chemoradiotherapy in stage III non‐small cell lung cancer

Real‐world experience of consolidation durvalumab after concurrent chemoradiotherapy in stage III non‐small cell lung cancer

Immunotherapy in unresectable stage III non-small-cell lung cancer: state of the art and novel therapeutic approaches

Anaplastic lymphoma kinase-special immunity and immunotherapy

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