108MO Safety and efficacy outcomes with durvalumab after sequential chemoradiotherapy (sCRT) in stage III, unresectable NSCLC (PACIFIC-6)

Garassino, M.C.; Mazieres, J.; Reck, Martin; Chouaïd, C.; Bischoff, H.; Reinmuth, Niels; Cove-Smith, Laura; Mansy, T.; Cortinovis, Diego; Migliorino, Maria Rita; Delmonte, Angelo; Sánchez, José García; Velarde, Luis Enrique Chara; Bernabé, R.; Paz-Ares, L.; Perez, I. Diaz; Trunova, Nataliya; Foroutanpour, K.; Faivre‐Finn, C.

doi:10.1016/j.annonc.2022.02.135

Cited by 12 publications

(15 citation statements)

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“…Very similar to Landman, the rate of pneumonitis was also 15%, with one case of grade 5 pneumonitis (0.8%). With a 2-year OS of 66% and a median PFS of 20.1 months, these data, similar to other RWD studies [37][38][39][40], corroborate the PACIFIC results. The fact that PD-L1 negative patients had the same oncological outcome challenges the notion that these patients should be excluded from durvalumab therapy based on the disputed EMA decision [41].…”

Section: Discussionsupporting

confidence: 89%

“…The difference with respect to the most prominent side effects after thoracic irradiation, i.e., pneumonitis and esophagitis, is usually a factor of 2, in some cases even 10 [5,43], which is the reason why only 30% of the patients with stage III NSCLC are amenable to concomitant treatment [6]. In contrast, the recently presented PACIFIC-6 data also underline the safe application of durvalumab following sequential CRT in an elderly patient cohort with potentially reduced performance status [40].…”

Section: Discussionmentioning

confidence: 99%

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Durvalumab after Sequential High Dose Chemoradiotherapy versus Standard of Care (SoC) for Stage III NSCLC: A Bi-Centric Retrospective Comparison Focusing on Pulmonary Toxicity

Wass

Hochmair²,

Kaiser

et al. 2022

Cancers

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Introduction: The standard of care (SoC) for unresectable stage III non-small-cell lung cancer (NSCLC) is durvalumab maintenance therapy after concurrent chemoradiation in patients with PD-L1 > 1%. However, the concurrent approach is only amenable for about one-third of patients due to co-morbidities. Although sequential regimens are usually not regarded as curative, these schedules applied in a dose-escalated manner may be similarly radical as SoC. As combining high-dose radiation and durvalumab remains a question of debate this retrospective bi-center study aims to evaluate pulmonary toxicity after high-dose chemoradiotherapy beyond 70 Gy compared to SoC. Patients and Methods: Patients with NSCLC stage III received durvalumab after either sequential high-dose chemoradiation or concomitant SoC. Chemotherapy consisted of platinum combined with either pemetrexed, taxotere, vinorelbine, or gemcitabine. The primary endpoint was short-term pulmonary toxicity occurring within six months after the end of radiotherapy (RT). Results: A total of 78 patients were eligible for this analysis. 18F-FDG-PET-CT, cranial MRT, and histological/cytological verification were mandatory in the diagnostic work-up. The high-dose and SoC group included 42/78 (53.8%) and 36/78 (46.2%) patients, respectively, which were matched according to baseline clinical variables. While the interval between the end of RT and the start of durvalumab was equal in both groups (p = 0.841), more courses were administered in the high-dose cohort (p = 0.031). Pulmonary toxicity was similar in both groups (p = 0.599), whereas intrathoracic disease control was better in the high-dose group (local control p = 0.081, regional control p = 0.184). Conclusion: The data of this hypothesis-generating study suggest that sequential high-dose chemoradiation followed by durvalumab might be similar to SoC in terms of pulmonary toxicity and potentially more effective with respect to intra-thoracic disease control. Larger trials with a prospective design are warranted to validate these results.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Durvalumab after Sequential High Dose Chemoradiotherapy versus Standard of Care (SoC) for Stage III NSCLC: A Bi-Centric Retrospective Comparison Focusing on Pulmonary Toxicity

Wass

Hochmair²,

Kaiser

et al. 2022

Cancers

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“…Given that many patients are not candidates for concurrent chemoradiation, the phase 2 PACIFIC-6 trial is assessing the safety of durvalulmab after sequential chemoradiation. Data presented in 2022 showed similar safety to that seen in the PACIFIC trial suggesting that this may also represent a reasonable treatment strategy in patients unable to undergo concurrent chemoradiation ( 64 ). In the phase II COAST study, durvalumab was combined with olecumab (anti-CD73 mAb) or monalizumab (anti-NKG2A mAb) as consolidative treatment of unresectable stage III NSCLC after concurrent chemoradiation.…”

Section: The Current Immunotherapy Landscape For the Treatment Of Nsclcmentioning

confidence: 73%

Immunotherapy in non-small cell lung cancer: Past, present, and future directions

et al. 2022

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Many decades in the making, immunotherapy has demonstrated its ability to produce durable responses in several cancer types. In the last decade, immunotherapy has shown itself to be a viable therapeutic approach for non-small cell lung cancer (NSCLC). Several clinical trials have established the efficacy of immune checkpoint blockade (ICB), particularly in the form of anti-programmed death 1 (PD-1) antibodies, anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibodies and anti-programmed death 1 ligand (PD-L1) antibodies. Many trials have shown progression free survival (PFS) and overall survival (OS) benefit with either ICB alone or in combination with chemotherapy when compared to chemotherapy alone. The identification of biomarkers to predict response to immunotherapy continues to be evaluated. The future of immunotherapy in lung cancer continues to hold promise with the development of combination therapies, cytokine modulating therapies and cellular therapies. Lastly, we expect that innovative advances in technology, such as artificial intelligence (AI) and machine learning, will begin to play a role in the future care of patients with lung cancer.

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“…It should be noted that only 2.6% of the patients enrolled in the study had a PS ¼ 2. 17 Usually patients with PS 0/1 are fit enough to receive CCRT; reasons for receiving SCRT instead of CCRT should be elucidated, since patients receiving SCRT for logistic reasons and patients not fit enough for CCRT comprise two different populations, and it could be that they would derive a different benefitdand different AEsdfrom immunotherapy. Frailer patients are more prone to develop toxicities during CRT, and we can speculate that their immune system might be more severely impaired by CRT jeopardizing immunotherapy efficacy.…”

Section: Consolidation Immune Therapy After Concurrent or Sequential Crtmentioning

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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108MO Safety and efficacy outcomes with durvalumab after sequential chemoradiotherapy (sCRT) in stage III, unresectable NSCLC (PACIFIC-6)

Cited by 12 publications

References 0 publications

Durvalumab after Sequential High Dose Chemoradiotherapy versus Standard of Care (SoC) for Stage III NSCLC: A Bi-Centric Retrospective Comparison Focusing on Pulmonary Toxicity

Durvalumab after Sequential High Dose Chemoradiotherapy versus Standard of Care (SoC) for Stage III NSCLC: A Bi-Centric Retrospective Comparison Focusing on Pulmonary Toxicity

Immunotherapy in non-small cell lung cancer: Past, present, and future directions

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

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