Efficacy and long-term survival of advanced lung adenocarcinoma patients with uncommon EGFR mutations treated with 1st generation EGFR-TKIs compared with chemotherapy as first-line therapy

Lung Cancer ◽  
2019 ◽  
Vol 130 ◽  
pp. 42-49 ◽  
Author(s):  
Haixia Li ◽  
Chenyu Wang ◽  
Ziqi Wang ◽  
Yabo Hu ◽  
Guowei Zhang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Egfr Mutations ◽  
First Line ◽  
Term Survival ◽  
Long Term Survival ◽  
First Line Therapy ◽  
Line Therapy ◽  
Egfr Tkis

scholarly journals Cost-Effectiveness of Pembrolizumab Plus Chemotherapy Versus Pembrolizumab Monotherapy in Metastatic Non-Squamous and Squamous NSCLC Patients With PD-L1 Expression ≥ 50%

2022 ◽  
Vol 12 ◽  
Author(s):  
Qiao Liu ◽  
Zhen Zhou ◽  
Xia Luo ◽  
Lidan Yi ◽  
Liubao Peng ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Life Expectancy ◽  
Cost Effective ◽  
Base Case ◽  
First Line ◽  
Term Survival ◽  
First Line Therapy ◽  
Line Therapy ◽  
Nsclc Patients

Objective To compare the cost-effectiveness of the combination of pembrolizumab and chemotherapy (Pembro+Chemo) versus pembrolizumab monotherapy (Pembro) as the first-line treatment for metastatic non-squamous and squamous non-small-cell lung cancer (NSCLC) with PD-L1expression ≥50%, respectively, from a US health care perspective.Material and Methods A comprehensive Makrov model were designed to compare the health costs and outcomes associated with first-line Pembro+Chemo and first-line Pembro over a 20-years time horizon. Health states consisted of three main states: progression-free survival (PFS), progressive disease (PD) and death, among which the PFS health state was divided into two substates: PFS while receiving first-line therapy and PFS with discontinued first-line therapy. Two scenario analyses were performed to explore satisfactory long-term survival modeling.Results In base case analysis, for non-squamous NSCLC patients, Pembro+Chemo was associated with a significantly longer life expectancy [3.24 vs 2.16 quality-adjusted life-years (QALYs)] and a substantially greater healthcare cost ($341,237 vs $159,055) compared with Pembro, resulting in an ICER of $169,335/QALY; for squamous NSCLC patients, Pembro+Chemo was associated with a slightly extended life expectancy of 0.22 QALYs and a marginal incremental cost of $3,449 compared with Pembro, resulting in an ICER of $15,613/QALY. Our results were particularly sensitive to parameters that determine QALYs. The first scenario analysis yielded lower ICERs than our base case results. The second scenario analysis founded Pembro+Chemo was dominated by Pembro.Conclusion For metastatic non-squamous NSCLC patients with PD-L1 expression ≥50%, first-line Pembro+Chemo was not cost-effective when compared with first-line Pembro. In contrast, for the squamous NSCLC patient population, our results supported the first-line Pembro+Chemo as a cost-effective treatment. Although there are multiple approaches that are used for extrapolating long-term survival, the optimal method has yet to be determined.

scholarly journals Clinical factors associated with treatment outcomes in EGFR mutant non-small cell lung cancer patients with brain metastases: a case-control observational study

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Yung-Hsuan Chen ◽  
Yen-Fu Chen ◽  
Chung-Yu Chen ◽  
Jin-Yuan Shih ◽  
Chong-Jen Yu
Keyword(s):  
Brain Metastases ◽  
Egfr Mutations ◽  
First Line ◽  
Factors Associated ◽  
Brain Radiotherapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Nsclc Patients ◽  
Egfr Tki ◽  
Egfr Tkis

Abstract Background Non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations often develop brain metastases. Treatment with EGFR-tyrosine kinase inhibitors (TKIs) has shown the effectiveness; however, knowledge of the clinical factors associated with outcomes in NSCLC patients with EGFR mutations remains limited. Methods Treatment-naive patients diagnosed with advanced non-squamous NSCLC with brain metastases harboring EGFR mutations and treated with an EGFR-TKI as first-line therapy were enrolled with analysis of their medical records. Results A total of 134 advanced NSCLC patients with brain metastases harboring EGFR mutations received an EGFR-TKI (gefitinib: 62, erlotinib: 49, and afatinib: 23) as the first-line therapy. Sixty-nine had exon 19 deletions (51.5%), and 56 (41.8%) had L858R mutations. There was no statistically significant difference in progression-free survival (PFS) and overall survival (OS) among the EGFR-TKIs. Significantly shorter OS was noted in patients with multiple brain metastases (hazard ratio [HR]: 2.43, p = 0.007), uncommon EGFR mutations (HR: 3.75, p = 0.009), and liver metastases. Thirty-eight patients (29.1%) received brain radiotherapy for brain metastases before disease progression, and had a significantly longer time until intracranial progression. However, the brain radiotherapy had no statistically significant impact on PFS or OS. Conclusions Patients with uncommon mutations, multiple brain metastases, and concomitant liver metastases tended to have shorter OS. Brain radiotherapy could delay the time to intracranial disease progression but had no impact on survival. The different first-line EGFR-TKIs achieved similar treatment responses in terms of PFS and OS in the EGFR-mutated NSCLC patients with brain metastases.

scholarly journals Primary Pelvic Exenteration for Advanced Gynaecological Malignancies

2020 ◽  
Vol 25 (2) ◽  
pp. 52-54
Author(s):  
Dragoș Constantin Cucoranu ◽  
Raluca Niculescu ◽  
Mihai Emil Căpîlna
Keyword(s):  
Pelvic Exenteration ◽  
Levator Ani ◽  
First Line ◽  
Term Survival ◽  
First Line Therapy ◽  
Line Therapy ◽  
Pelvic Malignancies ◽  
Advanced Stages ◽  
Gynaecological Malignancies

AbstractIntroduction: Indication of primary pelvic exenteration, without previous radiotherapy, is questionable in advanced stages of gynaecological malignancies.Materials and Methods: 24 patients who underwent primary pelvic exenteration for pelvic malignancies were studied retrospectively. The indications were cervical (n=17), vaginal (n=4), bladder (n=2) and endometrial cancer (n=1).Results: According to the type of exenteration, 14 were anterior and 10 total. Relying on the resection lines in relation with levator ani muscles, 14 were supralevatorial and 10 infralevatorial, of which five involved vulvectomy. Early complications occurred in 7 patients with 1 perioperative death.Conclusions: Primary pelvic exenterantion as first line therapy for advanced gynaecological malignancies can lead to long-term survival and it can even be curative in suitable selected patients. Still, postoperative complications are frequent, which can be lethal.

scholarly journals A Case Report of EGFR-mutated Metastatic Lung Adenocarcinoma with Long-term Survival on Systemic Treatment

2021 ◽  
Vol 1 (1) ◽  
pp. 51-58
Author(s):  
Daniel Dulf ◽  
Paul Kubelak ◽  
Dana Iancu ◽  
Tudor-Eliade Ciuleanu
Keyword(s):  
Lung Adenocarcinoma ◽  
Egfr Mutations ◽  
Term Survival ◽  
Metastatic Lung ◽  
Cellular Pathways ◽  
Long Term Survivors ◽  
Egfr Mutated ◽  
Egfr Tkis ◽  
Systemic Therapies

"Metastatic non-small cell lung cancer has historically been associated with a poor prognosis. The introduction of targeted agents against certain molecules involved in cellular pathways has shown improved responses, but long-term survivors are still rare. We present the case of a patient with lung adenocarcinoma harboring sensitizing EGFR mutations who showed an impressive survival of more than 9 years following a combination of systemic therapies consisting of cytotoxic drugs and EGFR TKIs that were very well tolerated."

scholarly journals The New ELN Recommendations for Treating CML

2020 ◽  
Vol 9 (11) ◽  
pp. 3671
Author(s):  
Rüdiger Hehlmann
Keyword(s):  
Kinase Inhibitors ◽  
Chronic Phase ◽  
Cost Effective ◽  
Low Grade ◽  
Molecular Response ◽  
First Line ◽  
Term Survival ◽  
First Line Therapy ◽  
Line Therapy

After normal survival has been achieved in most patients with chronic myeloid leukemia (CML), a new goal for treating CML is survival at good quality of life, with treatment discontinuation in sustained deep molecular response (DMR; MR4 or deeper) and treatment-free remission (TFR). Four tyrosine kinase inhibitors (TKIs) have been approved for first-line therapy: imatinib, dasatinib, nilotinib, bosutinib. Unexpectedly, the outcome of long-term randomized trials has shown that faster response as achieved by higher doses of imatinib, imatinib in combination, or second-generation (2G)-TKIs, does not translate into a survival advantage. Serious and frequent, and in part cumulative long-term toxicities, have led to a reevaluation of the role of 2G-TKIs in first-line therapy. Generic imatinib is the current most cost-effective first-line therapy in the chronic phase. A change of treatment is recommended when intolerance cannot be ameliorated or molecular milestones are not reached. Patient comorbidities and contraindications of all TKIs must be considered. Risk profile at diagnosis should be assessed with the EUTOS score for long-term survival (ELTS). Monitoring of response is by polymerase chain reaction (PCR). Cytogenetics is still required in the case of atypical translocations, atypical transcripts, and additional chromosomal aberrations. TKIs are contraindicated during pregnancy. Since the majority of patients are at risk of lifelong exposure to TKIs, amelioration of chronic low-grade side effects is important.

scholarly journals The Co-Expression of Programmed Death-Ligand 1 (PD-L1) in Untreated EGFR-Mutated Metastatic Lung Adenocarcinoma

Biomedicines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 36 ◽  
Author(s):  
Ping-Chih Hsu ◽  
Chih-Wei Wang ◽  
Scott Chih-Hsi Kuo ◽  
Shu-Min Lin ◽  
Yu-Lun Lo ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Objective Response ◽  
First Line ◽  
Programmed Death Ligand 1 ◽  
First Line Therapy ◽  
Line Therapy ◽  
Programmed Death ◽  
Metastatic Lung ◽  
Egfr Mutated ◽  
Egfr Tkis

Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) is the standard first-line therapy for metastatic lung adenocarcinoma harboring sensitive EGFR mutations. Tumor surface programmed death-ligand 1 (PD-L1) is expressed in some metastatic EGFR-mutated lung adenocarcinoma, but its impact on the efficacy of EGFR-TKIs is unclear. We retrospectively investigated 117 untreated metastatic lung EGFR mutated adenocarcinoma patients with a PD-L1 immunohistochemistry test. The PD-L1 expression level was classified by tumor proportion scores (TPS). Forty-five patients had negative expression (TPS < 1%), 45 had a weak expression (TPS 1–49%), and 27 had a strong expression (≥50%). All patients recruited in this study received EGFR-TKIs as a first-line therapy. No significant differences were observed for objective response rates (68.9% versus 62.2% versus 73.1%, p = 0.807) and median time to treatment failure (TTF) (12.17 versus 13.17 versus 11.0 months, p = 0.443) of first-line EGFR-TKIS among the three groups of patients (negative versus weak versus strong). The median overall survival was 21.27 versus 20.63 versus 19.43 months among the three groups of patients (p = 0.77). Our results demonstrated that PD-L1 did not affect the efficacy of first-line EGFR-TKIs in metastatic EGFR mutated lung adenocarcinoma. Thus, EGFR-TKIs are suggested as the preferred clinical therapy for these patients, despite their PD-L1 levels.

scholarly journals Not BCL2 mutation but dominant mutation conversation contributed to acquired venetoclax resistance in acute myeloid leukemia

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Xiang Zhang ◽  
Jiejing Qian ◽  
Huafeng Wang ◽  
Yungui Wang ◽  
Yi Zhang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Underlying Mechanism ◽  
Lymphocytic Leukemia ◽  
First Line ◽  
Dominant Mutation ◽  
First Line Therapy ◽  
Line Therapy ◽  
Acute Myeloid

AbstractVenetoclax (VEN) plus azacitidine has become the first-line therapy for elderly patients with acute myeloid leukemia (AML), and has a complete remission (CR) plus CR with incomplete recovery of hemogram rate of ≥70%. However, the 3-year survival rate of these patients is < 40% due to relapse caused by acquired VEN resistance, and this remains the greatest obstacle for the maintenance of long-term remission in VEN-sensitive patients. The underlying mechanism of acquired VEN resistance in AML remains largely unknown. Therefore, in the current study, nine AML patients with acquired VEN resistance were retrospectively analyzed. Our results showed that the known VEN resistance-associated BCL2 mutation was not present in our cohort, indicating that, in contrast to chronic lymphocytic leukemia, this BCL2 mutation is dispensable for acquired VEN resistance in AML. Instead, we found that reconstructed existing mutations, especially dominant mutation conversion (e.g., expanded FLT3-ITD), rather than newly emerged mutations (e.g., TP53 mutation), mainly contributed to VEN resistance in AML. According to our results, the combination of precise mutational monitoring and advanced interventions with targeted therapy or chemotherapy are potential strategies to prevent and even overcome acquired VEN resistance in AML.

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