SAKK 19/17: safety analysis of first-line durvalumab in patients with PD-L1 positive, advanced nonsmall cell lung cancer and a performance status of 2

Mark, Michael; Froesch, Patrizia; Eboulet, Eric Innocents; Addeo, Alfredo; Pless, Miklos; Rothschild, Sacha I.; Janthur, Wolf-Dieter; Burmeister, Henning; Friedlaender, Alex; Schneider, Martina; Metaxas, Y.; Joerger, Markus; Wannesson, Luciano; Schwitter, Michael; Baudoux, Nathalie; Weindler, Susanne; Biaggi-Rudolf, Christine; Früh, Martin

doi:10.1007/s00262-020-02757-8

Cited by 15 publications

(9 citation statements)

References 37 publications

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“…The data demonstrate that using first-line durvalumab in patients with PS2 and metastatic NSCLC with PD-L1 expression ⩾25% resulted in an unexpectedly high number of fatal early events due to rapid tumour progression. 68 All the clinical data described here are summarised in Table 2.…”

Section: Pd-1/pd-l1 Inhibitors As First-line Treatment Of Advanced Nsclcmentioning

confidence: 99%

The progress and challenge of anti-PD-1/PD-L1 immunotherapy in treating non-small cell lung cancer

Mei

Liu

et al. 2021

Ther Adv Med Oncol

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The use of programmed cell-death protein 1 (PD-1)/programmed cell-death ligand 1 (PD-L1) inhibitors is the standard therapy for the first-line or second-line treatment of patients with non-small-cell lung cancer (NSCLC). In contrast to current traditional treatments such as chemotherapy or radiotherapy, anti-PD-1 and anti-PD-L1 treatments can directly attenuate tumour-mediated exhaustion and effectively modulate the host anti-tumour immune response in vivo. In addition, compared with traditional therapy, PD-1/PD-L1 inhibitor monotherapy can significantly prolong survival without obvious side effects in the treatment of advanced NSCLC. Ideally, several biomarkers could be used to monitor the safety and effectiveness of anti-PD-1 and anti-PD-L1 treatments; however, the current lack of optimal prognostic markers remains a widespread limitation and challenge for further clinical applications, as does the possibility of immune-related adverse events and drug resistance. In this review, we aimed to summarise the latest progress in anti-PD-1/anti-PD-L1 treatment of advanced NSCLC, worldwide, including in China. An exploration of underlying biomarker identification and future challenges will be discussed in this article to facilitate translational studies in cancer immunotherapy.

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Section: Pd-1/pd-l1 Inhibitors As First-line Treatment Of Advanced Nsclcmentioning

confidence: 99%

The progress and challenge of anti-PD-1/PD-L1 immunotherapy in treating non-small cell lung cancer

Mei

Liu

et al. 2021

Ther Adv Med Oncol

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“…On the other hand indeed, Mark et al recently reported the interim safety analysis of the phase 2 SAKK 19/17 trial, enrolling PS 2 NSCLC patients with a PD-L1 ≥25% to receive durvalumab. This unplanned analysis has been solicited by the early death rate observed among the first 21 treated patients (63). Relevant exclusion criteria were the presence of active brain metastases and the concomitant treatment with steroids at the dose of > 10 mg daily of prednisone or equivalent.…”

Section: Prospective Trials With Anti-pd-1/pd-l1 Agents For Ps 2 Nsclc Patientsmentioning

confidence: 99%

First-line immunotherapy in non-small cell lung cancer patients with poor performance status: a systematic review and meta-analysis

Facchinetti¹,

Maïo²,

Perrone³

et al. 2021

Transl Lung Cancer Res

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Background: Immune checkpoint inhibitors (ICIs) have become the standard of care for the first-line treatment of advanced non-small cell lung cancer patients (NSCLC), either as single agents or combined with chemotherapy. The evidence sustaining their role for poor performance status (ECOG PS ≥2) patients is limited. Methods:We search PubMed and the proceedings of international oncology meetings to perform a systematic review to assess the outcomes poor PS NSCLC patients who received ICIs as first-line treatment.A meta-analysis included retrospective studies focusing on pembrolizumab monotherapy in PD-L1 ≥50% NSCLC. We reported the global objective response rate (ORR), disease control rate (DCR) and landmark progression-free and overall survival (PFS and OS, respectively) in ECOG PS ≥2 and 0-1 patients, respectively.Results: Forty-one studies were included in the systematic review. Thirty-two retrospective studies focused on pembrolizumab monotherapy in PD-L1 ≥50% cases. 1030 out of 5357 (19%) of patients across 30 studies presented with a PS ≥2 at pembrolizumab initiation. In 18 studies with detailed clinical information, worse outcomes in poor PS compared to good PS patients were documented. The meta-analysis revealed that ORR and DCR within the PS ≥2 patient population were 30.9% and 41.5% respectively (55.2% and 71.5% in PS 0-1 patients). The rates of PFS (at three, six, 12 and 18 months) and OS (at six, 12, 18 and 24 months) were approximately double in the good PS compared to the poor PS group of patients. In the three prospective trials where of ICIs in PS 2 populations, the diverse strictness in PS definition likely contributed to the differential outcomes observed. Six retrospective studies dealt with chemo-immunotherapy combinations.Conclusions: Still with limited prospective evidence sustaining the role of immunotherapy in previously untreated NSCLC with poor PS, 19% of patients in retrospective series dealing with pembrolizumab in PD-L1 ≥50% tumors had an ECOG PS ≥2. Clinical effort encompassing the definition of poor PS, of the factors conditioning it, and the development of dedicated treatment strategies is required to improve the outcomes in this patient population.

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“…Tumor‐directed therapy needs to be carefully recommended in solid tumors with a poor PS. 5 , 6 Therefore, it is important to find an effective prognostic indicator for patients with different PS to start to triage and choose the most appropriate treatments as well as rehabilitation interventions.…”

Section: Introductionmentioning

confidence: 99%

Handgrip weakness, systemic inflammation indicators, and overall survival in lung cancer patients with well performance status: A large multicenter observational study

et al. 2022

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Background Systemic inflammation and handgrip weakness have been used to predict mortality in many cancers. The purpose of current study was to evaluate the association of co‐occurrence of inflammation indicators and handgrip weakness with overall survival (OS) of lung cancer (LC) patients with good performance status. Methods The cutoff points for handgrip strength (HGS) and the four inflammation indicators were calculated using Maxstat. The time‐dependent receiver operating characteristic curve and C‐index were used to select optimal inflammation indicator for predicting OS of LC patients. The Cox proportional hazard regression model was used to calculate the hazard ratio (HR) of mortality. Kaplan–Meier curves were constructed to evaluate the association of indicators and the OS of LC patients. Results Among the 1951 patients, the mean ± standard deviation (SD) age was 60.6 ± 9.9 years, and 1300 (66.6%) patients were male. In patients with good performance status (PS), handgrip weakness (HR, 1.49; 95% confidence interval [95% CI], 1.30–1.70, p < 0.001) and low advanced lung cancer inflammation index (ALI) (HR, 2.05; 95%CI, 1.79–2.34, p < 0.001), high systemic immune‐inflammation index (SII) (HR, 1.91; 95%CI, 1.66–2.19, p < 0.001), high platelet: lymphocyte ratio (PLR) (HR, 1.60; 95%CI, 1.40–1.82, p < 0.001), or high neutrophil: lymphocyte ratio (NLR) (HR, 2.01; 95%CI, 1.76–2.30, p < 0.001) were associated with increased mortality risk of LC patients. ALI had better C‐index (0.624) and time‐AUC in the prediction of OS in LC patients with good PS than other three combinations. The co‐occurrence of handgrip weakness and low ALI more than doubled the risk of death in LC with good PS (HR, 2.44; 95% CI, 2.06–2.89, p < 0.001). Conclusion In LC patients who have good PS, patients with combined handgrip weakness and low ALI have the worst prognosis. The Trial Registration Number ChiCTR1800020329.

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SAKK 19/17: safety analysis of first-line durvalumab in patients with PD-L1 positive, advanced nonsmall cell lung cancer and a performance status of 2

Cited by 15 publications

References 37 publications

The progress and challenge of anti-PD-1/PD-L1 immunotherapy in treating non-small cell lung cancer

The progress and challenge of anti-PD-1/PD-L1 immunotherapy in treating non-small cell lung cancer

First-line immunotherapy in non-small cell lung cancer patients with poor performance status: a systematic review and meta-analysis

Handgrip weakness, systemic inflammation indicators, and overall survival in lung cancer patients with well performance status: A large multicenter observational study

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