Treatment of elderly patients or patients who are performance status 2 (PS2) with advanced Non-Small Cell Lung Cancer without epidermal growth factor receptor ( EGFR ) mutations and anaplastic lymphoma kinase ( ALK ) translocations – Still a daily challenge

Su, Chunxia; Zhou, Fei; Shen, Jiaxu; Zhao, Jing; O’Brien, Mary

doi:10.1016/j.ejca.2017.07.002

Cited by 21 publications

(13 citation statements)

References 114 publications

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“…sictr, control siRNA; siCD44, CD44 siRNA; p, phosphorylated; EGFR, epidermal growth factor receptor. chemotherapy in EGFR wild-type NSCLC tumors remains poor (22). Cisplatin, a commonly used chemotherapeutic, is widely used for treatment of NSCLC patients, while both its cytotoxicity and effective dose are relatively high (23).…”

Section: Discussionmentioning

confidence: 99%

CD44 inhibition attenuates EGFR signaling and enhances cisplatin sensitivity in human EGFR wild‑type non‑small‑cell lung cancer cells

Yin

Zhang

et al. 2020

Int J Mol Med

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cluster of differentiation 44 (cd44) as a transmembrane glycoprotein is found to be expressed in non-small cell lung cancer (NSCLC), is significantly associated with NSLC progression, metastasis and drug resistance. This study aimed to explore whether CD44 inhibition improves the sensitivity of epidermal growth factor receptor (EGFR) wild-type NSCLC cells to cisplatin and how it affects wild-type EGFR in NSCLC cells. Small interfering RNA was used to knockdown CD44 expression in EGFR wild-type NSCLC cell line H460. Results suggested that CD44 downregulation reduced cell growth, promoted G 0 /G 1 cell cycle arrest and induced cell apoptosis in H460 cells and these effects were evidently enhanced when in combination with cisplatin. Deactivation of EGFR signaling pathway including EGFR phosphorylation and its downstream molecules, targets ERK, AKT1 and SRC which were also observed in CD44-silenced H460 cells with or without EGF stimulation. Furthermore, the CD44 expression level was positively correlated with wild-type EGFR level in human lung adenocarcinoma tissues and CD44 inhibition significantly accelerated the degradation of EGFR, indicating that enhanced sensitivity of H460 cells to cisplatin by downregulation of CD44 might be due to EGFR degradation. This study demonstrated that suppression of CD44 deactivated EGFR signals in NSCLC cells with wild-type EGFR, thereby contributing to the inhibition of cell proliferation and the reinforcement of cisplatin sensitivity. It is suggested that downregulation of CD44 could be a novel potential therapeutic strategy for the treatment of EGFR wild-type NScLc.

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Section: Discussionmentioning

confidence: 99%

CD44 inhibition attenuates EGFR signaling and enhances cisplatin sensitivity in human EGFR wild‑type non‑small‑cell lung cancer cells

Yin

Zhang

et al. 2020

Int J Mol Med

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“…A combination of several factors has been described as a possible reason for why medical oncologists offer PC to poor performance status patients. These factors include: (i) physicians overestimate prognosis of metastatic cancer patients [26]; (ii) limited evidenced-based treatment recommendations in this scenario [27]; (iii) patients’ and families’ expectations to receive anti-cancer therapy [23]; (iv) young or middle-aged patients [28]; (v) absence of palliative care team participating in the patients care [29]; and (vi) care at an academic/ teaching hospital [24]. Our cohort was composed mainly of treatment naïve patients who were admitted in an academic cancer center due to symptoms related to advanced solid tumor disease.…”

Section: Discussionmentioning

confidence: 99%

Inpatient palliative chemotherapy is associated with high mortality and aggressive end-of-life care in patients with advanced solid tumors and poor performance status

et al. 2019

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Background The benefit of palliative chemotherapy (PC) in patients with advanced solid tumors and poor performance status (ECOG-PS) has not been prospectively validated, which makes treatment decision challenging. We aimed to evaluate the overall survival, factors associated with early mortality, and adoption of additional procedures in hospitalized patients with advanced cancer and poor ECOG-PS treated with PC. Methods We analyzed a retrospective cohort of patients with advanced cancer treated with PC during hospitalization at an academic cancer center in Brazil from 2014 to 2016. Eligibility criteria included: ECOG-PS 3–4 and start of first-line PC; or ECOG-PS ≥ 2 and start of second or subsequent lines. Primary endpoint was 30-day survival from start of PC. Kaplan-Meier method was used for survival estimates and Cox regression for factors associated with 30-day mortality. Results Two hundred twenty-eight patients were eligible. 21.9, 66.7 and 11.4% of patients had ECOG-PS 2, 3 and 4, respectively. 49.6% had gastrointestinal tumors. Median follow-up was 49 days (range 1–507). 98.2% of patients had died, 32% during the index hospitalization. The 30-day and 60-day survival rates were 55.7 and 38.5%, respectively. 30% of patients were admitted to the intensive care unit. In a multivariable analysis, ECOG-PS 3/4 (HR 2.01; P = 0.016), hypercalcemia (HR 2.19; P = 0.005), and elevated bilirubin (HR 3.17; P < 0.001) were significantly associated with 30-day mortality. Conclusions Patients with advanced cancer and poor ECOG-PS had short survival after treatment with inpatient PC. Inpatient PC was associated with aggressive end-of-life care. Prognostic markers such as ECOG-PS, hypercalcemia and elevated bilirubin can contribute to the decision-making process for these patients.

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“…While it is a known negative prognostic factor for survival, its predictive significance with ICIs is less clear. Instinctively, as chemotherapy improves outcomes in patients with PS2, one would want to extend the benefit to less toxic ICIs, and not undertreat these patients [6]. Unfortunately, data on the efficacy of ICIs in patients with PS2 are scant, stemming mainly from small trials, subgroup analyses or expanded access registries [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Impact of performance status on non-small-cell lung cancer patients with a PD-L1 tumour proportion score ≥50% treated with front-line pembrolizumab

et al. 2020

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Objectives: We retrospectively analysed patients with advanced non-small-cell lung cancer (NSCLC) harbouring high PD-L1 expression (>50%) and treated with front-line pembrolizumab, comparing outcomes of patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2 to those with PS 0-1. Methods: Data were collected by 16 participating centres. All patients with NSCLC and high PD-L1, treated with first-line pembrolizumab were included. We collected medical data from patient files, pathology and laboratory reports. Patient characteristics, comorbidities, PS, and tumour characteristics were reported. Overall survival (OS), progression-free survival (PFS) and response rate (RR) were calculated. Results: 302 patients were included, 246 with PS 0-1, 56 with PS 2. RR was 72% among patients with PS 0-1 compared to 45% with PS2 (odds ratio (OR) 0.31 (95% CI: 0.17-0.57), p < .001). Median PFS was 2.6 months (95% CI: 1.9-5.1) among patients with PS2 and 11.3 months (95% CI: 8.5-14.4) among those with PS 0-1. Median OS was 7.8 months (95% CI: 2.5-10.7) in the PS2 group, not reached in the PS 0-1 group. PS 2 remained predictive of poor outcomes in multivariate analysis. Conclusion: PS 2 is a strong independent predictor of poor response and survival in NSCLC patients with high PD-L1, treated with front-line pembrolizumab. Prospective randomised trials comparing immunotherapy to chemotherapy in this population would be welcome.

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Treatment of elderly patients or patients who are performance status 2 (PS2) with advanced Non-Small Cell Lung Cancer without epidermal growth factor receptor ( EGFR ) mutations and anaplastic lymphoma kinase ( ALK ) translocations – Still a daily challenge

Cited by 21 publications

References 114 publications

CD44 inhibition attenuates EGFR signaling and enhances cisplatin sensitivity in human EGFR wild‑type non‑small‑cell lung cancer cells

CD44 inhibition attenuates EGFR signaling and enhances cisplatin sensitivity in human EGFR wild‑type non‑small‑cell lung cancer cells

Inpatient palliative chemotherapy is associated with high mortality and aggressive end-of-life care in patients with advanced solid tumors and poor performance status

Impact of performance status on non-small-cell lung cancer patients with a PD-L1 tumour proportion score ≥50% treated with front-line pembrolizumab

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