Progression-Free and Overall Survival for Concurrent Nivolumab With Standard Concurrent Chemoradiotherapy in Locally Advanced Stage IIIA-B NSCLC: Results From the European Thoracic Oncology Platform NICOLAS Phase II Trial (European Thoracic Oncology Platform 6-14)

Peters, Solange; Felip, Enriqueta; Dafni, Urania; Tufman, Amanda; Gückenberger, Matthias; Álvarez, Ruth; Nadal, Ernest; Becker, Annemarie; Vees, Hansjörg; Pless, Miklos; Martinez-Martí, Alex; Lambrecht, Maarten; Andratschke, Nicolaus; Tsourti, Zoi; Piguet, Anne‐Christine; Roschitzki-Voser, Heidi; Gasca-Ruchti, A.; Vansteenkiste, Johan; Stahel, Rolf A.; Ruysscher, Dirk De

doi:10.1016/j.jtho.2020.10.129

Cited by 102 publications

(73 citation statements)

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“…Two studies on CRT combined with concurrent and/or sequential anti-PD-1 inhibitors (LUN 14-179 and NICO-LAS) reported a significantly lower PFS and OS in patients with UICC 7th edition stage IIIB disease [6,7,25,26]. In our study, the subgroup of patients with both PTV ≥ 900ccm Considering the apparent limitations of our analysis, namely its single-center design, limited patient number and a median follow-up of 19.9 months, it is of potential interest Fig.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, the ground-breaking PACIFIC phase III trial demonstrated a three-year survival rate of 57% and a median PFS of 16.8 months [9,10]. In addition, the first clinical reports on chemoradioimmunotherapy have confirmed the PACIFIC findings concerning patient outcome [7,[11][12][13].…”

Section: Introductionmentioning

confidence: 86%

“…Regarding inoperable stage III NSCLC, the implementation of CPI as one of the key components of a multimodal approach has already led to an unprecedented improvement in progression-free survival (PFS) and OS [5][6][7][8]. In particular, the ground-breaking PACIFIC phase III trial demonstrated a three-year survival rate of 57% and a median PFS of 16.8 months [9,10].…”

Section: Introductionmentioning

confidence: 99%

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Planning target volume as a predictor of disease progression in inoperable stage III non-small cell lung cancer patients treated with chemoradiotherapy and concurrent and/or sequential immune checkpoint inhibition

et al. 2021

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SummaryBackground. The present study evaluates outcome after chemoradiotherapy (CRT) with concurrent and/or sequential Programmed Cell Death 1 (PD-1) or Ligand 1 (PD-L1) immune checkpoint inhibition (CPI) for inoperable stage III NSCLC patients depending on planning target volume (PTV). Method and patients. Prospective data of thirty-three consecutive patients with inoperable stage III NSCLC treated with CRT and sequential durvalumab (67%, 22 patients) or concurrent and sequential nivolumab (33%, 11 patients) were analyzed. Different PTV cut offs and PTV as a continuous variable were evaluated for their association with progression-free (PFS), local–regional progression-free (LRPFS), extracranial distant metastasis-free (eMFS) and brain-metastasis free-survival (BMFS). Results. All patients were treated with conventionally fractionated thoracic radiotherapy (TRT); 93% to a total dose of at least 60 Gy, 97% of patients received two cycles of concurrent platinum-based chemotherapy. Median follow-up for the entire cohort was 19.9 (range: 6.0–42.4) months; median overall survival (OS), LRFS, BMFS and eMFS were not reached. Median PFS was 22.8 (95% CI: 10.7–34.8) months. Patients with PTV ≥ 900ccm had a significantly shorter PFS (6.9 vs 22.8 months, p = 0.020) and eMFS (8.1 months vs. not reached, p = 0.003). Furthermore, patients with PTV ≥ 900ccm and stage IIIC disease (UICC-TNM Classification 8th Edition) achieved a very poor outcome with a median PFS and eMFS of 3.6 vs 22.8 months (p < 0.001) and 3.6 months vs. not reached (p = 0.001), respectively. PTV as a continuous variable also had a significant impact on eMFS (p = 0.048). However, no significant association of different PTV cut-offs or PTV as a continuous variable with LRPFS and BMFS could be shown. The multivariate analysis that was performed for PTV ≥ 900ccm and age (≥ 65 years), gender (male), histology (non-ACC) as well as T- and N-stage (T4, N3) as covariates also revealed PTV ≥ 900ccm as the only factor that had a significant correlation with PFS (HR: 5.383 (95% CI:1.263–22.942, p = 0.023)). Conclusion. In this prospective analysis of inoperable stage III NSCLC patients treated with definitive CRT combined with concurrent and/or sequential CPI, significantly shorter PFS and eMFS were observed in patients with initial PTV ≥ 900ccm.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

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Planning target volume as a predictor of disease progression in inoperable stage III non-small cell lung cancer patients treated with chemoradiotherapy and concurrent and/or sequential immune checkpoint inhibition

et al. 2021

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“…When ICIs have been assessed as consolidation agents following standard of care definitive (chemo-)radiotherapy for locally advanced disease, RT has been delivered mostly in a conventional dose-fractionation schedule (1.8-2 Gy per fraction, one fraction per day, five days per week, to a total of 60-66 Gy for NSCLC) ( 2 , 41 , 42 ). The rationale behind this schedule is based on the linear quadratic model, whereby the optimal dose-fractionation regimen in order to kill cancer cells while sparing surrounding normal tissues may be established.…”

Section: Controversies About Dose and Fractionationmentioning

confidence: 99%

Radiotherapy in the Era of Immunotherapy With a Focus on Non-Small-Cell Lung Cancer: Time to Revisit Ancient Dogmas?

et al. 2021

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Radiation-induced immune effects have been extensively deciphered over the last few years, leading to the concept of the dual immune effect of radiotherapy with both immunostimulatory and immunosuppressive effects. This explains why radiotherapy alone is not able to drive a strong anti-tumor immune response in most cases, hence underlining the rationale for combining both radiotherapy and immunotherapy. This association has generated considerable interest and hundreds of trials are currently ongoing to assess such an association in oncology. However, while some trials have provided unprecedented results or shown much promise, many hopes have been dashed. Questions remain, therefore, as to how to optimize the combination of these treatment modalities. This narrative review aims at revisiting the old, well-established concepts of radiotherapy relating to dose, fractionation, target volumes and organs at risk in the era of immunotherapy. We then propose potential innovative approaches to be further assessed when considering a radio-immunotherapy association, especially in the field of non-small-cell lung cancer (NSCLC). We finally propose a framework to optimize the association, with pragmatic approaches depending on the stage of the disease.

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“…The NICOLAS study was the first completed single-armed phase 2 clinical trial with the participation of 79 stage III NSCLC patients [30]. The study evaluated the efficacy of nivolumab (360 mg every 3 weeks) along with platinum-based chemotherapy (3 cycles) with concurrent radiotherapy (66 Gy, 33 fractions).…”

Section: Practical Aspects Of the Use Of Combination Therapy With Radiotherapy Chemotherapy And Immunotherapy In Nsclc Patientsmentioning

confidence: 99%

Molecular and Clinical Premises for the Combination Therapy Consisting of Radiochemotherapy and Immunotherapy in Non-Small Cell Lung Cancer Patients

Frąk¹,

Krawczyk²,

Kalinka³

et al. 2021

Cancers

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Non-small cell lung cancer (NSCLC) is one of the most common malignancies around the world. Due to the advanced stage of the disease at the time of diagnosis, most patients require systemic treatment. Immunotherapy with immune checkpoints inhibitors is becoming the main treatment method for many cancers, including NSCLC. Numerous studies have shown greater efficacy of immunotherapy used monoclonal antibodies anti-PD-1 (pembrolizumab and nivolumab) or anti-PD-L1 (atezolizumab and durvalumab) compared to chemotherapy. Unfortunately, cancer cells can develop a number of mechanisms to escape from immune surveillance, including avoidance of cancer cells by the immune system (immune desert), production of immunosuppressive compounds (prostaglandins, IDO, TGF-beta), or direct immune checkpoints interactions. Therapy based on the use of radiochemotherapy with subsequent immunotherapy is becoming the main focus of research in the field of new NSCLC therapies. Radiation therapy stimulates the immune response multidirectionally, affects production of neoantigens and proinflammatory compounds, which transform non-immunogenic (“cold”) tumors into highly immunogenic (“hot”) tumors. As a result, the mechanisms of escape of cancer cells from immune surveillance break down and the effectiveness of immunotherapy increases significantly. The results of clinical trials in this area bring new hope and indicate greater effectiveness of such treatment in terms of prolongation of progression-free survival and overall survival.

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Progression-Free and Overall Survival for Concurrent Nivolumab With Standard Concurrent Chemoradiotherapy in Locally Advanced Stage IIIA-B NSCLC: Results From the European Thoracic Oncology Platform NICOLAS Phase II Trial (European Thoracic Oncology Platform 6-14)

Cited by 102 publications

References 13 publications

Planning target volume as a predictor of disease progression in inoperable stage III non-small cell lung cancer patients treated with chemoradiotherapy and concurrent and/or sequential immune checkpoint inhibition

Planning target volume as a predictor of disease progression in inoperable stage III non-small cell lung cancer patients treated with chemoradiotherapy and concurrent and/or sequential immune checkpoint inhibition

Radiotherapy in the Era of Immunotherapy With a Focus on Non-Small-Cell Lung Cancer: Time to Revisit Ancient Dogmas?

Molecular and Clinical Premises for the Combination Therapy Consisting of Radiochemotherapy and Immunotherapy in Non-Small Cell Lung Cancer Patients

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