Targeted therapy and elderly people: A review

Daste, Amaury; Chakiba, Camille; Domblides, Charlotte; Gross‐Goupil, Marine; Quivy, Amandine; Ravaud, Alain; Soubeyran, Pierre

doi:10.1016/j.ejca.2016.10.005

Cited by 36 publications

(25 citation statements)

References 113 publications

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“…The majority of observational research in older patients with HER2+ breast cancer has focused on early-stage disease [14]. There are few data from observational studies on the treatment and outcomes for older patients with HER2 + MBC and in the present study we sought to describe the real-world treatment patterns and survival outcomes for patients ≥ 65 starting trastuzumab for HER2 + MBC.. Our specific objectives were to determine the: time-on-trastuzumab and other HER2-targeted therapies; time-on-other cancer therapies; patterns of cardiac monitoring; and OS in this older population.…”

Section: Introductionmentioning

confidence: 99%

Trastuzumab use in older patients with HER2-positive metastatic breast cancer: outcomes and treatment patterns in a whole-of-population Australian cohort (2003–2015)

et al. 2019

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Background Older patients with HER2-positive metastatic breast (HER2 + MBC) cancer are underrepresented in clinical trials. We aim to describe the treatment patterns and overall survival (OS) for older women receiving trastuzumab for HER2 + MBC. Methods Retrospective, whole-of-population cohort study using demographic, dispensing, and medical services data for Australian women ≥ 65 years initiating trastuzumab for HER2 + MBC between 2003 and 2015. We describe time-on-trastuzumab; type and timing of other cancer treatments; rates of cardiac monitoring; and OS from trastuzumab initiation for HER2 + MBC. Results Of 5404 women initiating trastuzumab for HER2 + MBC, 1583 (29%) were ≥ 65 years old, and the proportion of older patients increased from 20% in 2003 to 38% in 2015. The median age for older women was 73 years and 516 (33%) were ≥ 75 years. Most older patients (92%) received ≥3medicines for comorbidities other than cancer. Median (IQR) time on trastuzumab was 14.1 months (5.9–32.1) and on all chemotherapy was 5.6 months (3.3–10.8). 74% received ≥1 chemotherapy agent and 56% received endocrine therapy. Half (49%) of patients had a cardiac assessment prior to initiating trastuzumab and overall 1228 (76%) had ≥1 cardiac assessment during the study period. At a median follow-up of 6 years, 73% of patients had died and the median OS was 25.6 months (IQR 10.7–58.7). Conclusions Older patients comprise a growing proportion of patients treated with HER2-targeted therapies in the real-world but they remain underrepresented in trials of these agents. Few trials report duration or OS estimates for older patients but our estimates are similar to those from trials that have. Although cardiac monitoring was a requirement of accessing trastuzumab during our study period, many patients did not undergo a cardiac assessment.

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Section: Introductionmentioning

confidence: 99%

Trastuzumab use in older patients with HER2-positive metastatic breast cancer: outcomes and treatment patterns in a whole-of-population Australian cohort (2003–2015)

et al. 2019

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“…Targeted therapy is a therapeutic method that specifically targets certain cancer-related genes or proteins [5, 6]. Since the expression of these genes or proteins may be abnormal in specific cancers, they could be potential biomarkers for these cancers.…”

Section: Introductionmentioning

confidence: 99%

RAB10 overexpression promotes tumor growth and indicates poor prognosis of hepatocellular carcinoma

Wang

Jia

et al. 2017

Oncotarget

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Hepatocellular carcinoma (HCC), one of the most common and lethal cancers worldwide, has a high recurrence rate with current treatment modalities. Identifying biomarkers for early diagnosis and discovering new sufficient molecular targets for the development of targeted therapies are urgently needed. RAB10, a member of the RAS family, has been shown to be highly expressed in HCC. However, the function of RAB10 in HCC is less studied. Here we report that RAB10 acts as an oncogene in HCC. The shRNA-mediated knockdown of RAB10 significantly reduced the proliferation of HCC cells and colony formation, induced cell cycle arrest at G0/G1 phase and increased apoptosis in vitro. In addition, RAB10 knockdown suppressed HCC growth in nude mice. Moreover, RAB10 silencing decreased the phosphorylation of InsR, Met/HGFR, Ron/MST1R, Ret, c-Kit/SCFR, EphA3, EphB4, Tyro3/Dtk, Axl, Tie2/TEK, VEGFR2/KDR, Akt/PKB/Rac, S6 Ribosomal Protein and c-Abl, while the phosphorylation of HSP27, p38 MAPK, Chk2 and TAK1 increased significantly. These results suggest that RAB10 regulates cell survival and proliferation through multiple oncogenic, cell stress and apoptosis pathways. More importantly, high RAB10 expression levels in HCC cells correlated with a poor prognosis in HCC patients. Therefore, our findings revealed an oncogenic role for RAB10 in the pathogenesis of HCC and that RAB10 is a potential molecular target or a biomarker for HCC.

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“…In a review of 1,178 patients by Daste et al in 2016, it was reported that ALK rearrangements tended to be present in NSCLC patients with no smoking habit (29). DiBonaventura et al reported treatment of 207 patients, including a median age of 60 and 25 (12%) current smokers (30).…”

Section: Discussionmentioning

confidence: 99%

“…It is considered difficult to conduct clinical trials of TKI in the elderly patients from the viewpoint of accumulation of patients because of the rarity of this disease. At present, however, as TKIs such as alectinib with fewer side-effects exist, administration is feasible (29,30), and it might be desirable to perform the same TKI treatment as in younger patients.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological Features in Elderly ALK-rearranged Non-small Cell Lung Cancer Patients

Miyazaki¹,

Sato²,

Kodama³

et al. 2020

In Vivo

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Aim: To clarify the clinicopathological features in elderly anaplastic lymphoma kinase (ALK) rearranged non-small cell lung cancer (NSCLC) patients. Patients and Methods: A retrospective study was performed in 129 ALK rearranged NSCLC patients diagnosed between April 2008 and March 2019 in fifteen Institutions of the Ibaraki prefecture, Japan. Results: Median age of patients was 63 years. In 59 patients aged 65 and older, the proportions of patients with advanced stage and those treated with ALKtyrosine kinase inhibitor (TKI) were lower than those younger than 65 years. There was no difference in overall survival (OS) between the two age groups. Among the elderly patients, no difference was observed in OS between the patients aged 65-69 and those aged 70 and older. In 89 patients treated with TKI, no significant differences were observed in the progression-free survival of TKIs and OS between patients aged 65 and older and those younger than 65, respectively. Conclusion: Evaluation of ALK gene status and TKI treatment are desirable even for elderly patients. Advances in molecular biology have led to discovery of specific driver genes in certain cancer types and therefore to development of specific therapeutics (1, 2). This new trend is evident in the clinical practice of NSCLC patients. Mutations in the anaplastic lymphoma kinase (ALK) fusion gene is one such driver gene. Long-term survival can be expected in ALKrearranged NSCLC patients, but its frequency is very rare (1, 2001 This article is freely accessible online.

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Targeted therapy and elderly people: A review

Cited by 36 publications

References 113 publications

Trastuzumab use in older patients with HER2-positive metastatic breast cancer: outcomes and treatment patterns in a whole-of-population Australian cohort (2003–2015)

Trastuzumab use in older patients with HER2-positive metastatic breast cancer: outcomes and treatment patterns in a whole-of-population Australian cohort (2003–2015)

RAB10 overexpression promotes tumor growth and indicates poor prognosis of hepatocellular carcinoma

Clinicopathological Features in Elderly ALK-rearranged Non-small Cell Lung Cancer Patients

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