Treatment outcome and safety of anti-PD-1 antibody against elderly non-small cell lung cancer.

e14249 Background: The anti-PD-1 antibodies, Pembrolizumab (Pem) and Nivolumab (Nivo), have become available for practical clinical use in Japan, and many patients are benefiting from them. Lung cancer is predominantly a disease of the elderly people. However, the validity and safety of anti-PD-1 antibodies against the elderly are insufficient. Methods: From February 2016 to November 2018, 66 patients with non-small cell lung cancer who received anti-PD-1 antibody therapy (23 Pem and 43 Nivo) were evaluated for progression-free survival (PFS), overall survival (OS), and safety were compared between groups between the aged ≥75 years (≥75 yrs) and < 75 years ( < 75 yrs). Results: The median age (width) was 67 years (46-87 years). 46 patients were < 75 yrs and 20 patients were ≥75 yrs. PFS was 3.3 months (m) vs. 4.4 m ( < 75 yrs vs. ≥75 yrs)(p = 0.214). OS was 11.7 m vs. 16.7 m ( < 75 yrs vs. ≥75 yrs)(p = 0.212). Similar analysis was carried out for each anti-PD-1 antibody. In Pem, 15 patients were < 75 yrs and 8 patients were ≥75 yrs, and there was no significant difference between PFS and OS (p = 0.46, p = 0.17, respectively). In Nivo, 31 patients < 75 yrs, 12 patietns > 75 yrs, and there was no significant difference in PFS and OS (p = 0.49, p = 0.44, respectively). Immunity-related adverse events (irAE) was expressed in 25 patients (37.9%). Among 66 patients, 19 in 46 (41%) were < 75 yrs, 6 in 20 (30%) were ≥75yrs. There were not many irAEs even in the elderly people (χ2= 0.757, p = 0.384). Conclusions: Pem and Nivo proved to be effective and safe for the elderly patients even in the clinical setting.

Download Full-text

Immune Checkpoint Inhibitor Outcomes for Patients With Non–Small-Cell Lung Cancer Receiving Baseline Corticosteroids for Palliative Versus Nonpalliative Indications

Journal of Clinical Oncology ◽

10.1200/jco.19.00189 ◽

2019 ◽

Vol 37 (22) ◽

pp. 1927-1934 ◽

Cited By ~ 58

Author(s):

Biagio Ricciuti ◽

Suzanne E. Dahlberg ◽

Anika Adeni ◽

Lynette M. Sholl ◽

Mizuki Nishino ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Progression Free Survival ◽

Small Cell ◽

Small Cell Lung ◽

Corticosteroid Administration ◽

Programmed Cell Death 1 ◽

Significant Difference ◽

Poor Outcomes

PURPOSE Baseline use of corticosteroids is associated with poor outcomes in patients with non–small-cell lung cancer (NSCLC) treated with programmed cell death-1 axis inhibition. To approach the question of causation versus correlation for this association, we examined outcomes in patients treated with immunotherapy depending on whether corticosteroids were administered for cancer-related palliative reasons or cancer-unrelated indications. PATIENTS AND METHODS Clinical outcomes in patients with NSCLC treated with immunotherapy who received ≥ 10 mg prednisone were compared with outcomes in patients who received 0 to < 10 mg of prednisone. RESULTS Of 650 patients, the 93 patients (14.3%) who received ≥ 10 mg of prednisone at the time of immunotherapy initiation had shorter median progression-free survival (mPFS) and median overall survival (mOS) times than patients who received 0 to < 10 mg of prednisone (mPFS, 2.0 v 3.4 months, respectively; P = .01; mOS, 4.9 v 11.2 months, respectively; P < .001). When analyzed by reason for corticosteroid administration, mPFS and mOS were significantly shorter only among patients who received ≥ 10 mg prednisone for palliative indications compared with patients who received ≥ 10 mg prednisone for cancer-unrelated reasons and with patients receiving 0 to < 10 mg of prednisone (mPFS, 1.4 v 4.6 v 3.4 months, respectively; log-rank P < .001 across the three groups; mOS, 2.2 v 10.7 v 11.2 months, respectively; log-rank P < .001 across the three groups). There was no significant difference in mPFS or mOS in patients receiving ≥ 10 mg of prednisone for cancer-unrelated indications compared with patients receiving 0 to < 10 mg of prednisone. CONCLUSION Although patients with NSCLC treated with ≥ 10 mg of prednisone at the time of immunotherapy initiation have worse outcomes than patients who received 0 to < 10 mg of prednisone, this difference seems to be driven by a poor-prognosis subgroup of patients who receive corticosteroids for palliative indications.

Download Full-text

Comparison of efficiency and toxicity of two chemotherapy protocols in treatment of advanced non-small cell lung cancer

Medicinski pregled ◽

10.2298/mpns1108368m ◽

2011 ◽

Vol 64 (7-8) ◽

pp. 368-372 ◽

Cited By ~ 3

Author(s):

Alma Mekic-Abazovic ◽

Ibrahim Sisic ◽

Vladimir Kovcin ◽

Hakija Beculic ◽

Senad Dervisevic ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Tumour Response ◽

Progression Free Survival ◽

Small Cell ◽

Rank Test ◽

Small Cell Lung ◽

Free Survival ◽

Significant Difference

Introduction. This study was aimed at comparing the efficiency and tolerability of two reference protocols Cisplatin and Etoposide and Cisplatin and Vinorelbine in advanced Non-Small Cell Lung Cancer. Material and Methods. A total of 60 patients (two groups consisting of 30 patients) were treated for advanced Non-Small Cell Lung Cancer during the period from January to December 2005 according to the reference protocols (Cisplatin 100mg/m2 D1; Vinorelbine 30 mg/m2 D1, D8 on 4 weeks) and (Cisplatin 100 mg/m2 D1; Etoposide 100 mg/m2 D1, D3, D5 on 4 weeks) at the Department of Oncology of KBC ?Bezanijska kosa?. All patients were analyzed for tumour response, progression free survival as well as for toxicity. X2 test, Kaplan Meiers curves and Log rank test were used for statistical analysis. Results. Although the recorded response rates were a bit lower than in previously published trials, they were not significantly different p=0.485. No statistically significant difference was recorded in either progression free survival or overall survival. The chemotherapeutical Cisplatin/Etoposide protocol proved to be more toxic both in hematologic (3% vs. 10%) and total toxicities (p=0.047). Conclusion. Our study proved both protocols to have equivalent efficacy. However, the Cisplatin, Vinorelbine protocol could be recommended because of its less expressed toxic effects.

Download Full-text

EGFR Exon 18 Mutations in Advanced Non-Small Cell Lung Cancer: A Real-World Study on Diverse Treatment Patterns and Clinical Outcomes

Frontiers in Oncology ◽

10.3389/fonc.2021.713483 ◽

2021 ◽

Vol 11 ◽

Author(s):

Haiyan Xu ◽

Guangjian Yang ◽

Weihua Li ◽

Junling Li ◽

Xuezhi Hao ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Clinical Outcomes ◽

Cell Lung Cancer ◽

Kinase Inhibitor ◽

Progression Free Survival ◽

Small Cell ◽

Small Cell Lung ◽

Effective Treatment Option ◽

Significant Difference

BackgroundApproximately 3–5% of patients with epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) harbor exon 18 mutations. The appropriate treatment for such patients has not been clarified. The aim of this study was to investigate the response of patients with NSCLC harboring EGFR exon 18 mutations to different therapeutic options.MethodsBetween May 2014 and September 2020, the clinical outcomes of 82 patients harboring EGFR exon 18 mutations who received first-generation (1G) EGFR-tyrosine kinase inhibitor (TKI), second-generation (2G) EGFR-TKI afatinib, chemotherapy, and 1G TKI in combination with chemotherapy as the initial therapy were retrospectively analyzed.ResultsA total of 82 NSCLC patients harboring EGFR 18 mutations with whose treatment and survival outcomes were available were analyzed. The median age was 59 years, and 47 (57.3%) were female. The most common kind of EGFR exon 18 mutation was G719X (75.6%), followed by E709X (15.9%), E709_T710delinsD (3.6%), and other subtypes (4.9%). There was a significant difference in median progression-free survival (mPFS) by therapeutic strategy (P = 0.017). The mPFS of 1G TKI, 2G TKI afatinib, chemotherapy, and 1G TKI in combination with chemotherapy were 7.7 (95% CI, 4.2–11.2), 11.3 (95% CI, 5.6–17.0), 5.0 (95% CI, 2.3–17.7), and 11.1 (95% CI, 5.9–16.4) months, respectively. No significant difference in PFS was observed between afatinib and 1G TKI in combination with chemotherapy (P = 0.709).ConclusionsLike afatinib, 1G TKI in combination with chemotherapy might be an effective treatment option for patients harboring EGFR exon 18 mutations.

Download Full-text

Real-world outcomes after second-line treatment in non-small cell lung cancer (NSCLC) patients treated with immunotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e21620 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e21620-e21620

Author(s):

Melina Elpi Marmarelis ◽

Wei-Ting Hwang ◽

Yu-Xiao Yang ◽

Christine Agnes Ciunci ◽

Aditi Puri Singh ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Disease Progression ◽

Cell Lung Cancer ◽

Real World ◽

Progression Free Survival ◽

Small Cell ◽

Small Cell Lung ◽

National Guidelines ◽

Significant Difference

e21620 Background: In patients (pts) with advanced non-small cell lung cancer (NSCLC), national guidelines recommend against retrial of immunotherapy (IO) if there is disease progression on IO in the 1st-line (1L). However, optimal 2nd-line (2L) therapy after 1L IO remains unclear and there is significant practice variation. We compared outcomes of 2L approaches after 1L IO or chemoimmunotherapy (chemoIO). Methods: This retrospective cohort study utilized the Flatiron Health EHR-derived de-identified advanced NSCLC database. The study population included pts with disease progression on 1L IO or chemoIO and who subsequently received 2L therapy. Pts with targetable alterations were excluded. We defined the exposure by type of 2L therapy (IO, chemoIO, chemo). Multivariate covariates included age, sex, race, 1L progression-free survival (PFS) and PDL1 level. Median overall survival (mOS) and median real-world PFS (mPFS, based upon abstraction of clinician documentation) times were estimated from Kaplan-Meier curves. A multivariate Cox proportional hazard model computed hazard ratios (HRs) to assess the effectiveness of 2L treatment. Results: 532 NSCLC pts received 1L IO and a 2L therapy, of which 393 (74%) received 1L IO and 139 (26%) received 1L chemoIO. Among 1L IO patients, 2L therapies included chemo (315 (80%)), IO (39(10%), 18/39 (46%) switched IO), and chemoIO (39(10%)). Among 1L chemoIO patients, 2L therapies included: chemo (121 (87%)), IO (8(6%), 6/8 switched IO) and ChemoIO (10 (7%), 8/10 changed chemo used). All pts who received 2L ChemoIO continued the same IO agent. Demographics were well balanced between 2L groups except for higher PDL1 level in the IO-based groups and older age in the IO alone group. There was no statistically significant difference in mPFS or mOS between 2L IO and non-IO containing regimens (Table), nor were there differences among patients switching IO agents in the 2L (multivariate p interaction = 0.2 (PFS), 0.06 (OS)) (Table). Conclusions: Despite national guidelines against this practice, a small proportion of pts in routine care receive 2L IO-based therapies after disease progression on 1L IO or chemoIO. We found similar outcomes between IO and non-IO based 2L therapies after progression on 1L IO or chemoIO. [Table: see text]

Download Full-text

Predictive Factors for Poor Progression-free Survival in Patients with Non-small Cell Lung Cancer Treated with Nivolumab

10.21873/anticanres.12030 ◽

2017 ◽

Vol 37 (10) ◽

Cited By ~ 8

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Predictive Factors ◽

Cell Lung Cancer ◽

Progression Free Survival ◽

Small Cell ◽

Small Cell Lung ◽

Free Survival

Download Full-text

Selpercatinib in RET fusion-positive non-small-cell lung cancer (SIREN): a retrospective analysis of patients treated through an access program

Therapeutic Advances in Medical Oncology ◽

10.1177/17588359211019675 ◽

2021 ◽

Vol 13 ◽

pp. 175883592110196

Author(s):

Oliver Illini ◽

Maximilian Johannes Hochmair ◽

Hannah Fabikan ◽

Christoph Weinlinger ◽

Amanda Tufman ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Real World ◽

Objective Response ◽

Progression Free Survival ◽

Small Cell ◽

Small Cell Lung ◽

Real World Setting ◽

Access Program

Introduction: Rearranged during transfection (RET) gene fusions are rare genetic drivers in non-small cell lung cancer (NSCLC). Selective RET-inhibitors such as selpercatinib have shown therapeutic activity in early clinical trials; however, their efficacy in the real-world setting is unknown. Methods: A retrospective efficacy and safety analysis was performed on data from RET fusion-positive NSCLC patients who participated in a selpercatinib access program (named patient protocol) between August 2019 and January 2021. Results: Data from 50 patients with RET fusion-positive advanced NSCLC treated with selpercatinib at 27 centers in 12 countries was analyzed. Most patients were Non-Asian (90%), female (60%), never-smokers (74%), with a median age of 65 years (range, 38–89). 32% of the patients had known brain metastasis at the time of selpercatinib treatment. Overall, 13 patients were treatment-naïve, while 37 were pretreated with a median of three lines of therapy (range, 1–8). The objective response rate (ORR) was 68% [95% confidence interval (CI), 53–81] in the overall population. The disease control rate was 92%. The median progression-free survival was 15.6 months (95% CI, 8.8–22.4) after a median follow-up of 9 months. In patients with measurable brain metastases ( n = 8) intracranial ORR reached 100%. In total, 88% of patients experienced treatment-related adverse events (TRAEs), a large majority of them being grade 1 or 2. The most common grade ⩾ 3 TRAEs were increased liver enzyme levels (in 10% of patients), prolonged QTc time (4%), abdominal pain (4%), hypertension (4%), and fatigue/asthenia (4%). None of patients discontinued selpercatinib treatment for safety reasons. No new safety concerns were observed, nor where there any treatment-related death. Conclusions: In this real-world setting, the selective RET-inhibitor selpercatinib demonstrated durable systemic and intracranial antitumor activity in RET fusion-positive NSCLC and was well tolerated.

Download Full-text

SURG-05. IDEAL TREATMENT REGIMEN FOR PATIENTS WITH ≥1 BRAIN METASTASIS FROM PRIMARY NON-SMALL-CELL LUNG CANCER – A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS

Neuro-Oncology ◽

10.1093/neuonc/noaa215.852 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii204-ii204

Author(s):

Karanbir Brar ◽

Yosef Ellenbogen ◽

Behnam Sadeghirad ◽

Jiawen Deng ◽

Winston Hou ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Targeted Therapies ◽

Meta Analysis ◽

Performance Status ◽

Progression Free Survival ◽

Small Cell ◽

Small Cell Lung ◽

China National Knowledge Infrastructure

Abstract BACKGROUND Brain metastases (BM) are common in non-small cell lung cancer (NSCLC). The aim of this study was to assess the comparative effectiveness of treatments for BM from NSCLC. METHODS We searched MEDLINE, EMBASE, Web of Science, ClinicalTrials.gov, CENTRAL and references of key studies for randomized controlled trials (RCTs) published until October 2018. We also searched the Chinese databases Wanfang Data, Wanfang Med Online, China National Knowledge Infrastructure, and Chongqing VIP Information for RCTs published until September 2019. Trials including > 10 patients were selected. The primary outcomes were overall survival (OS) and intracranial progression-free survival (PFS). We used a frequentist random-effects model for network meta-analysis and assessed the certainty of evidence using the GRADE approach. RESULTS Among 8798 abstracts, 106 RCTs (9452 patients) met inclusion criteria. Median sample size was 67 (range 25-554). All trials included adult patients with histologically proven NSCLC and >1 BM proven on CT/MRI. Of trials that reported performance status (e.g. ECOG or KPS, n=67), 63/67 excluded patients with non-favorable performance status. Interventions assessed included surgery, WBRT, SRS, targeted therapies (i.e. EGFR/ALK inhibitors), and chemotherapy. Compared to WBRT alone, several interventions demonstrated a statistically significant increase in median OS, including non-targeted chemotherapy + surgery (MD: 415.3 days, 95% CI: 31.3-799.4), WBRT + EGFRi (MD: 200.2 days, 95% CI:146.3-254.1), and EGFRi alone (MD: 169.7 days, 95% CI: 49.7-289.7). Among all interventions, only WBRT + EGFRi showed a significant improvement in median PFS (MD: 108.0 days, 95%CI: 48.5-167.5). CONCLUSIONS Our preliminary analyses indicate an OS and PFS benefit on the addition of EGFR inhibitors to WBRT for the treatment of BMs from NSCLC. Further analyses of hazard ratios for OS/PFS are underway, and subgroup analyses are planned. These data support the growing role of targeted therapies in the treatment of BMs, particularly in susceptible mutant tumours.

Download Full-text

The Gustave Roussy Immune (GRIm)-Score Variation Is an Early-on-Treatment Biomarker of Outcome in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients Treated with First-Line Pembrolizumab

Journal of Clinical Medicine ◽

10.3390/jcm10051005 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1005

Author(s):

Edoardo Lenci ◽

Luca Cantini ◽

Federica Pecci ◽

Valeria Cognigni ◽

Veronica Agostinelli ◽

...

Keyword(s):

Lung Cancer ◽

Serum Albumin ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Objective Response ◽

Progression Free Survival ◽

Small Cell ◽

Albumin Concentration ◽

Small Cell Lung ◽

First Line

Background: The Gustave Roussy Immune (GRIm)-Score takes into account neutrophil-to-lymphocyte ratio (NLR), serum albumin concentration and lactate dehydrogenase (LDH) and its prognostic value has been investigated in patients treated with immune check-point inhibitors (ICIs). To further assess the prognostic and predictive value of baseline GRIm-Score (GRImT0) in advanced non-small cell lung cancer (aNSCLC) patients, we separately investigated two cohorts of patients treated with first-line pembrolizumab or chemotherapy. We also investigated whether GRIm-Score at 45 days since treatment initiation (GRImT1) and GRIm-Score difference between the two timepoints may better predict clinical outcomes (GRImΔ = GRImT0 − GRImT1). Methods: We retrospectively evaluated 222 aNSCLC patients: 135 treated with pembrolizumab and 87 treated with chemotherapy as the first-line regimen. NLR, serum albumin and LDH concentrations were assessed at T0 and at T1. According to the GRIm-Score, patients were assigned 1 point if they had NLR > 6, LDH > upper limit normal or albumin < 3.5 g/dL. Patients with a GRIm-Score < 2 were considered as having a low Score. Results: In both cohorts, no difference in terms of overall survival (OS) between patients with low and high GRImT0 was found. Otherwise, median OS and progression free survival (PFS) of the low GRImT1 group were significantly longer than those of the high GRImT1 group in pembrolizumab-treated patients, but not in the CHT cohort (pembrolizumab cohort: low vs. high; median OS not reached vs. 9.2 months, p = 0.004; median PFS 10.8 vs. 2.3 months, p = 0.002). Patients receiving pembrolizumab with stable/positive GRImΔ had better OS (median OS not reached vs. 12.0 months, p < 0.001), PFS (median PFS 20.6 vs. 2.6 months, p < 0.001) and objective response rate (58.2% vs. 7.6%, p = 0.003) compared to patients with negative GRImΔ. Conclusion: Our data shown that GRImT1 and GRImΔ are more reliable peripheral blood biomarkers of outcome compared to GRImT0 in aNSCLC patients treated with pembrolizumab and might represent useful biomarkers to drive clinical decisions in this setting.

Download Full-text

Digital Pathology and PD-L1 Testing in Non Small Cell Lung Cancer: A Workshop Record

Cancers ◽

10.3390/cancers12071800 ◽

2020 ◽

Vol 12 (7) ◽

pp. 1800 ◽

Cited By ~ 2

Author(s):

Fabio Pagni ◽

Umberto Malapelle ◽

Claudio Doglioni ◽

Gabriella Fontanini ◽

Filippo Fraggetta ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Gold Standard ◽

Digital Pathology ◽

Small Cell ◽

Small Cell Lung ◽

Significant Difference ◽

Standard Quality ◽

A Minor

A meeting among expert pathologists was held in 2019 in Rome to verify the results of the previous harmonization efforts on the PD-L1 immunohistochemical testing by scoring a representative series of non-small cell lung cancer (NSCLC) digital slides. The current paper shows the results of this digital experimental meeting and the expertise achieved by the community of Italian pathologists. PD-L1 protein expression was determined using tumor proportion score (TPS), i.e., the percentage of viable tumor cells showing partial or complete membrane staining at any intensity. The gold standard was defined as the final PD-L1 score formulated by a panel of seven lung committed pathologists. PD-L1 status was clustered in three categories, namely negative (TPS < 1), low (TPS 1–49%), and high (TPS ≥ 50%). In 23 cases (71.9%) PD-L1 staining was performed using the companion diagnostic 22C3 pharmDx kit on Dako Autostainer, while in nine (28.1%) cases it was performed using the SP263 Ventana kit on BenchMark platform. A complete PD-L1 scoring agreement between the panel of experts and the participants was reached in 57.1% of cases, whereas a minor disagreement in 16.1% of cases was recorded. Italian pathologists performed best in strong positive cases (i.e., tumor proportion score TPS > 50%), whereas only 10.8% of disagreement with the gold standard was observed, and 55.6% regarded a single challenging case. The worst performance was achieved in the negative cases, with 32.0% disagreement. A significant difference resulted from the analysis of the data separated by the different clones used: 22.3% and 38.1% disagreement (p = 0.01) was found in the group of cases analyzed by 22C3 and SP263 antibody clones, respectively. In conclusion, this workshop record proposed the application of a digital pathology platform to share controversial cases in educational meetings as an alternative possibility for improving the interpretation and reporting of specific histological tools. Due to the crucial role of PD-L1 TPS for the selection of patients for immunotherapy, the identification of unconventional approaches as virtual slides to focus experiences and give more detailed practical verifications of the standard quality reached may be a considerable option.

Download Full-text