Choosing wisely first line immunotherapy in non-small cell lung cancer (NSCLC): what to add and what to leave out

Proto, Claudia; Ferrara, Roberto; Signorelli, Diego; Russo, Giuseppe Lo; Galli, Giulia; Imbimbo, Martina; Prelaj, Arsela; Zilembo, Nicoletta; Ganzinelli, Monica; Pallavicini, L.; Simone, Irene De; Colombo, Mario P.; Sica, Antonio; Torri, Valter; Garassino, Marina Chiara

doi:10.1016/j.ctrv.2019.03.004

Cited by 139 publications

(98 citation statements)

References 77 publications

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“…However, a small number of patients respond to ICIs both in section-and first-line monotherapy in daily practice (about 25-30%) [1,17]. Moreover, the association of chemotherapy plus immunotherapy improved response and survival outcomes in the first-line setting, but toxicity rates doubled due to the addition of chemotherapy [7].…”

Section: Discussionmentioning

confidence: 99%

“…Pembrolizumab is currently the standard of care as first-line therapy in PD-L1 >50% aNSCLC [6]. Recently, combinations of ICIs with platinum-doublet chemotherapy (Keynote-189 and Keynote-407) and bevacizumab (IMpower150), as well as the association of nivolumab with Anti-Cytotoxic T-Lymphocyte Antigen 4 (anti-CTLA-4) agent ipilimumab (CheckMate 227), have shown survival benefit compared to standard chemotherapy, emerging as new treatment options for first-line setting in aNSCLC [7]. The introduction of these novel treatments in the clinical practice has generated several challenges, including the evidence of novel patterns of response and the management of new adverse events [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

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EPSILoN: A Prognostic Score for Immunotherapy in Advanced Non-Small-Cell Lung Cancer: A Validation Cohort

Prelaj

Ferrara

Rebuzzi

et al. 2019

Cancers

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Background: Beyond programmed death ligand 1 (PD-L1), no other biomarkers for immunotherapy are used in daily practice. We previously created EPSILoN (Eastern Cooperative Oncology Group performance status (ECOG PS), smoking, liver metastases, lactate dehydrogenase (LDH), neutrophil-to-lymphocyte ratio (NLR)) score, a clinical/biochemical prognostic score, in 154 patients treated with second/further-line immunotherapy. This study’s aim was to validate EPSILoN score in a different population group. Methods: 193 patients were included at National Cancer Institute of Milan (second-line immunotherapy, 61%; further-line immunotherapy, 39%). Clinical/laboratory parameters such as neutrophil-to-lymphocyte ratio and lactate dehydrogenase levels were collected. Kaplan–Meier and Cox hazard methods were used for survival analysis. Results: Overall median progression-free survival and median overall survival were 2.3 and 7.6 months, respectively. Multivariate analyses for Progression-Free Survival (PFS) identified heavy smokers (hazard ratio (HR) 0.71, p = 0.036) and baseline LDH < 400 mg/dL (HR 0.66, p = 0.026) as independent positive factors and liver metastases (HR 1.48, p = 0.04) and NLR ≥ 4 (HR 1.49, p = 0.029) as negative prognostic factors. These five factors were included in the EPSILoN score which was able to stratify patients in three different prognostic groups, high, intermediate and low, with PFS of 6.0, 3.8 and 1.9 months, respectively (HR 1.94, p < 0.001); high, intermediate and low prognostic groups had overall survival (OS) of 24.5, 8.9 and 3.4 months, respectively (HR 2.40, p < 0.001). Conclusions: EPSILoN, combining five baseline clinical/blood parameters (ECOG PS, smoking, liver metastases, LDH, NLR), may help to identify advanced non-small-cell lung cancer (aNSCLC) patients who most likely benefit from immune checkpoint inhibitors (ICIs).

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

EPSILoN: A Prognostic Score for Immunotherapy in Advanced Non-Small-Cell Lung Cancer: A Validation Cohort

Prelaj

Ferrara

Rebuzzi

et al. 2019

Cancers

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“…In addition, pembrolizumab and other ICIs combined with platinum or bevacizumab have become one of the first-line treatment of choice for NSCLC without oncogenic drivers, irrespective of PD-L1 expression. 17,18 The emergence of immunotherapy brings a new choice for lung cancer with poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

Unexpected favorable outcome to sintilimab plus bevacizumab in an EGFR‐mutated non‐small cell lung cancer patient: A case report

et al. 2020

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A 53‐year‐old man diagnosed with disease stage IIIB pulmonary adenocarcinoma underwent chemotherapy and radiotherapy in the first‐line setting. After disease progression, he received targeted therapy because of subsequent detection of EGFR exon 19 del mutation. Following an increase in his adrenal metastases, a combination of immunotherapy and antiangiogenic therapy (sintilimab plus bevacizumab) was commenced. After one month, imaging showed that the adrenal metastases had shrunk and a progression‐free survival (PFS) of 6.0 months was achieved. In this case, we showed that the PD1 inhibitor sintilimab plus bevacizumab was effective in a refactory advanced EGFR‐mutant NSCLC with positive PD‐L1 expression. Key points Our case report provides clinical evidence of the durable response of a patient with advanced EGFR‐mutant lung adenocarcinoma to a combination of immunotherapy and anti‐angiogenic agent, sintilimab and bevacizumab, as subsequent‐line therapy. Sintilimab and bevacizumab combination therapy was well‐tolerated and effective, resulting in dramatic tumor reduction and improvement in clinical symptoms.

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“…while platinum-based chemotherapy may represent only the rst-line option for patients with no PD-L1 expression and TMB-negative [62]. Nevertheless, the predictive value of TMB should be further investigated in future randomized trials.…”

Section: Sample Collectionmentioning

confidence: 99%

TERT Mutation was Associated with the Risk of Recurrence in Lung Adenocarcinoma with A Micropapillary Pattern

Wang

Li²,

Hao

et al. 2020

Preprint

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Abstract Background: Lung adenocarcinoma with a micropapillary pattern (MPPAC) is the histological subtype of lung cancer. It has attracted increasing attention, especially regarding its association with poor prognosis, including the predisposition towards recurrence and metastasis. Although MPPAC has been described in early-stage cases, only a few studies have reported the correlation between disease-specific prognosis and gene mutation of MPPAC. This study aimed to clarify the common genetic mutations and the prognostic characteristics in MPPAC patients.Methods: A total of 17 patients whose surgical pathology was defined as MPPAC were followed up, the molecular characteristics were elucidated by next-generation sequencing, and the prognostic characteristics were analyzed. Results: Epidermal growth factor receptor (EGFR) mutations were identified in 11/17 (65%) of patients. TP53 alterations were identified in 10/17 (59%). Other common mutations include ATM (18%), KRAS (18%), SDHA (18%), and TERT (18%). MPPAC patients harboring EGFR and TERT mutations were at a high risk of tumor recurrence, while TP53 might be associated with a low risk of recurrence. Conclusions: TERT mutation was more frequently harbored in MPPAC patients than in the other histological type of lung cancer, and such patients were at a high risk of recurrence. So TERT mutation might be associated with adverse prognosis in MPPAC patients.

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Choosing wisely first line immunotherapy in non-small cell lung cancer (NSCLC): what to add and what to leave out

Cited by 139 publications

References 77 publications

EPSILoN: A Prognostic Score for Immunotherapy in Advanced Non-Small-Cell Lung Cancer: A Validation Cohort

EPSILoN: A Prognostic Score for Immunotherapy in Advanced Non-Small-Cell Lung Cancer: A Validation Cohort

Unexpected favorable outcome to sintilimab plus bevacizumab in an EGFR‐mutated non‐small cell lung cancer patient: A case report

TERT Mutation was Associated with the Risk of Recurrence in Lung Adenocarcinoma with A Micropapillary Pattern

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