Abstract P079: The impact of BCL2 expression on sensitivity to the novel Aurora kinase B inhibitor AZD2811 in small cell lung cancer

Background: Although well established for the effective management of hematologic cancers, maintenance chemotherapy has only been recently incorportated as a treatment paradigm for advanced non–small-cell lung cancer. Maintenance chemotherapy aims to prolong a clinically favorable response state achieved after finishing induction therapy which is usually predefined in number before startng treatment. There are 2 modalities for maintenance therapy; continuation maintenance (involving a non-platinum component which was a part of the induction protocol or a targeted agent) and switch maintenance therapy (utilizing a new agent which was not a part of the induction regimen). Methods: The purpose of this article is to review the role of maintenance therapy in the treatment of advanced Non-Small Cell Lung Cancer (NSCLC) and provide a brief overview about induction chemotherapy in NSCLC to address the basis of maintenance therapy as a treatment option. We will also compare the impact of maintenance chemotherapy with the now evolving role of immunotherapy in NSCLC. Results: There have been 4 maintenance studies to date showing prolonged PFS and OS with statistical significance. However, Three out of the four studies (ECOG4599, JMEN, and PARAMOUNT) did not report tumor molecular analysis. As regard Immunotherapy, current data is in favour of strongly an increasing role for immunotherapy in NSCLC. Conclusion: Maintenance therapy in NSCLC continues to be an important therapeutic line to improve outcome in patients with metastatic and recurrent disease.

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The impact of reclassifying cancers of unspecified histology on international differences in survival for small cell and non‐small cell lung cancer ( ICBP SurvMark ‐2 project)

International Journal of Cancer ◽

10.1002/ijc.33620 ◽

2021 ◽

Author(s):

Eileen Morgan ◽

Melina Arnold ◽

Mark Rutherford ◽

Aude Bardot ◽

Jacques Ferlay ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Small Cell Lung ◽

International Differences ◽

The Impact

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479P The impact of initial symptoms on survival time in advanced non-small cell lung cancer

Annals of Oncology ◽

10.1016/s0923-7534(21)00637-2 ◽

2016 ◽

Vol 27 ◽

pp. ix153-ix154

Author(s):

T. Miyawaki ◽

S. Yagishita ◽

R. Ko ◽

Y. Suzuki ◽

N. Matsumoto ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Survival Time ◽

Cell Lung Cancer ◽

Small Cell ◽

Small Cell Lung ◽

Initial Symptoms ◽

The Impact

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Differential influence of antibiotic therapy and other medications on oncological outcomes of patients with non-small cell lung cancer treated with first-line pembrolizumab versus cytotoxic chemotherapy

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2021-002421 ◽

2021 ◽

Vol 9 (4) ◽

pp. e002421

Author(s):

Alessio Cortellini ◽

Massimo Di Maio ◽

Olga Nigro ◽

Alessandro Leonetti ◽

Diego L Cortinovis ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Objective Response ◽

Multivariable Analysis ◽

Small Cell ◽

Small Cell Lung ◽

First Line ◽

Metastatic Nsclc ◽

The Impact

BackgroundSome concomitant medications including antibiotics (ATB) have been reproducibly associated with worse survival following immune checkpoint inhibitors (ICIs) in unselected patients with non-small cell lung cancer (NSCLC) (according to programmed death-ligand 1 (PD-L1) expression and treatment line). Whether such relationship is causative or associative is matter of debate.MethodsWe present the outcomes analysis according to concomitant baseline medications (prior to ICI initiation) with putative immune-modulatory effects in a large cohort of patients with metastatic NSCLC with a PD-L1 expression ≥50%, receiving first-line pembrolizumab monotherapy. We also evaluated a control cohort of patients with metastatic NSCLC treated with first-line chemotherapy. The interaction between key medications and therapeutic modality (pembrolizumab vs chemotherapy) was validated in pooled multivariable analyses.Results950 and 595 patients were included in the pembrolizumab and chemotherapy cohorts, respectively. Corticosteroid and proton pump inhibitor (PPI) therapy but not ATB therapy was associated with poorer performance status at baseline in both the cohorts. No association with clinical outcomes was found according to baseline statin, aspirin, β-blocker and metformin within the pembrolizumab cohort. On the multivariable analysis, ATB emerged as a strong predictor of worse overall survival (OS) (HR=1.42 (95% CI 1.13 to 1.79); p=0.0024), and progression free survival (PFS) (HR=1.29 (95% CI 1.04 to 1.59); p=0.0192) in the pembrolizumab but not in the chemotherapy cohort. Corticosteroids were associated with shorter PFS (HR=1.69 (95% CI 1.42 to 2.03); p<0.0001), and OS (HR=1.93 (95% CI 1.59 to 2.35); p<0.0001) following pembrolizumab, and shorter PFS (HR=1.30 (95% CI 1.08 to 1.56), p=0.0046) and OS (HR=1.58 (95% CI 1.29 to 1.94), p<0.0001), following chemotherapy. PPIs were associated with worse OS (HR=1.49 (95% CI 1.26 to 1.77); p<0.0001) with pembrolizumab and shorter OS (HR=1.12 (95% CI 1.02 to 1.24), p=0.0139), with chemotherapy. At the pooled analysis, there was a statistically significant interaction with treatment (pembrolizumab vs chemotherapy) for corticosteroids (p=0.0020) and PPIs (p=0.0460) with respect to OS, for corticosteroids (p<0.0001), ATB (p=0.0290), and PPIs (p=0.0487) with respect to PFS, and only corticosteroids (p=0.0033) with respect to objective response rate.ConclusionIn this study, we validate the significant negative impact of ATB on pembrolizumab monotherapy but not chemotherapy outcomes in NSCLC, producing further evidence about their underlying immune-modulatory effect. Even though the magnitude of the impact of corticosteroids and PPIs is significantly different across the cohorts, their effects might be driven by adverse disease features.

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An evaluation of the impact of a multidisciplinary team, in a single centre, on treatment and survival in patients with inoperable non-small-cell lung cancer

Yearbook of Pulmonary Disease ◽

10.1016/s8756-3452(08)70372-4 ◽

2007 ◽

Vol 2007 ◽

pp. 150-152

Author(s):

L.T. Tanoue

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Multidisciplinary Team ◽

Small Cell ◽

Small Cell Lung ◽

Single Centre ◽

The Impact

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Outcome of patients with small-cell lung cancer: effect of changes in staging procedures and imaging technology on prognostic factors over 14 years.

Journal of Clinical Oncology ◽

10.1200/jco.1990.8.6.1042 ◽

1990 ◽

Vol 8 (6) ◽

pp. 1042-1049 ◽

Cited By ~ 42

Author(s):

M P Dearing ◽

S M Steinberg ◽

R Phelps ◽

M J Anderson ◽

J L Mulshine ◽

...

Keyword(s):

Lung Cancer ◽

Prognostic Factors ◽

Brain Metastases ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Cox Proportional Hazards ◽

Small Cell ◽

Small Cell Lung ◽

Limited Stage ◽

The Impact

In a study of 411 patients with small-cell lung cancer (SCLC) entered on therapeutic clinical trials between 1973 and 1987, we analyzed whether changes in the prognostic importance of pretreatment factors had occurred during the 14-year time period. After adjusting for other prognostic factors, brain involvement was associated with shorter survival in patients treated before December 1979 (P = .024) but not in patients treated thereafter (P = .54). The patients diagnosed before 1979 had brain metastases documented by radionuclide scan while computed cranial tomography (CCT) was more commonly used after 1979. Patients who had brain metastases diagnosed by radionuclide scan lived a shorter period of time than patients who had the diagnosis made by the more sensitive CCT scan (P = .031). In contrast, Cox proportional hazards modeling showed that liver metastases in patients were associated with shorter survival in patients treated after 1979 (P = .0007) but not in patients treated before then (P = .30). A larger proportion of patients had a routine liver biopsy before 1979 than after 1979 when more patients had the liver staged with less sensitive imaging studies and biochemical parameters. Patients with SCLC whose cancer was confined to the thorax but had medical or anatomic contraindications to intensive chest radiotherapy had similar survival compared with patients with limited-stage SCLC who were treated with combination chemotherapy alone (P = .68). From these data we conclude: (1) the sensitivity of the staging procedures used can affect the impact on survival of cancer involvement of a given site; and (2) patients with cancer confined to their chest with medical or anatomic contraindications to chest radiotherapy do not have a shorter survival than patients with limited-stage disease treated with chemotherapy alone.

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The impact of non-tumor-derived circulating nucleic acids implicates the prognosis of non-small cell lung cancer

Journal of Cancer Research and Clinical Oncology ◽

10.1007/s00432-012-1300-5 ◽

2012 ◽

Vol 139 (1) ◽

pp. 67-76 ◽

Cited By ~ 17

Author(s):

Chanida Vinayanuwattikun ◽

Pakorn Winayanuwattikun ◽

Poonchavist Chantranuwat ◽

Apiwat Mutirangura ◽

Virote Sriuranpong

Keyword(s):

Lung Cancer ◽

Nucleic Acids ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Small Cell Lung ◽

Circulating Nucleic Acids ◽

The Impact

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Pemetrexed Versus Pemetrexed and Carboplatin As Second-Line Chemotherapy in Advanced Non–Small-Cell Lung Cancer: Results of the GOIRC 02-2006 Randomized Phase II Study and Pooled Analysis With the NVALT7 Trial

Journal of Clinical Oncology ◽

10.1200/jco.2012.43.6758 ◽

2012 ◽

Vol 30 (36) ◽

pp. 4501-4507 ◽

Cited By ~ 31

Author(s):

Andrea Ardizzoni ◽

Marcello Tiseo ◽

Luca Boni ◽

Andrew D. Vincent ◽

Rodolfo Passalacqua ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Advanced Nsclc ◽

Pooled Analysis ◽

Small Cell ◽

Second Line ◽

Small Cell Lung ◽

Platinum Based Chemotherapy ◽

The Impact

Purpose To compare efficacy of pemetrexed versus pemetrexed plus carboplatin in pretreated patients with advanced non–small-cell lung cancer (NSCLC). Patients and Methods Patients with advanced NSCLC, in progression during or after first-line platinum-based chemotherapy, were randomly assigned to receive pemetrexed (arm A) or pemetrexed plus carboplatin (arm B). Primary end point was progression-free survival (PFS). A preplanned pooled analysis of the results of this study with those of the NVALT7 study was carried out to assess the impact of carboplatin added to pemetrexed in terms of overall survival (OS). Results From July 2007 to October 2009, 239 patients (arm A, n = 120; arm B, n = 119) were enrolled. Median PFS was 3.6 months for arm A versus 3.5 months for arm B (hazard ratio [HR], 1.05; 95% CI, 0.81 to 1.36; P = .706). No statistically significant differences in response rate, OS, or toxicity were observed. A total of 479 patients were included in the pooled analysis. OS was not improved by the addition of carboplatin to pemetrexed (HR, 90; 95% CI, 0.74 to 1.10; P = .316; P heterogeneity = .495). In the subgroup analyses, the addition of carboplatin to pemetrexed in patients with squamous tumors led to a statistically significant improvement in OS from 5.4 to 9 months (adjusted HR, 0.58; 95% CI, 0.37 to 0.91; P interaction test = .039). Conclusion Second-line treatment of advanced NSCLC with pemetrexed plus carboplatin does not improve survival outcomes as compared with single-agent pemetrexed. The benefit observed with carboplatin addition in squamous tumors may warrant further investigation.

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