24 research outputs found
HIV-1 Tat immunization restores immune homeostasis and attacks the HAART-resistant blood HIV DNA: results of a randomized phase II exploratory clinical trial
Implementation of immunotherapy in the treatment of advanced non-small cell lung cancer (NSCLC)
Mechanisms of tumor immune surveillance and immune escape have been
recently elucidated and led to the development of a new therapeutic
field in oncology, that of immunotherapy. Immunotherapy aims to
reactivate the immune system against cancer. Neoplasias like non-small
cell lung cancer (NSCLC) are of particular interest and clinical studies
with immunotherapeutic agents have shown significant survival benefit.
Several agents have gained corresponding regulatory approvals. In
particular, nivolumab, pembrolizumab and atezolizumab have been approved
for second-line treatment of NSCLC, pembrolizumab is the only immune
checkpoint inhibitor that has been approved in the first-line treatment
and durvalumab is approved in the locally advanced disease. In this
review, we aim to present the implementation of immunotherapy in the
treatment of advanced NSCLC. We will discuss not only the approved
regimens but also the future perspectives, the serious adverse events
such as hyperprogression and the possible predictive markers that will
aid the selection of the patients that will benefit from immunotherapy
Implementation of immunotherapy in the treatment of advanced non-small cell lung cancer (NSCLC)
Implementation of immunotherapy in the treatment of advanced non-small cell lung cancer (NSCLC)
Mechanisms of tumor immune surveillance and immune escape have been
recently elucidated and led to the development of a new therapeutic
field in oncology, that of immunotherapy. Immunotherapy aims to
reactivate the immune system against cancer. Neoplasias like non-small
cell lung cancer (NSCLC) are of particular interest and clinical studies
with immunotherapeutic agents have shown significant survival benefit.
Several agents have gained corresponding regulatory approvals. In
particular, nivolumab, pembrolizumab and atezolizumab have been approved
for second-line treatment of NSCLC, pembrolizumab is the only immune
checkpoint inhibitor that has been approved in the first-line treatment
and durvalumab is approved in the locally advanced disease. In this
review, we aim to present the implementation of immunotherapy in the
treatment of advanced NSCLC. We will discuss not only the approved
regimens but also the future perspectives, the serious adverse events
such as hyperprogression and the possible predictive markers that will
aid the selection of the patients that will benefit from immunotherapy
Treating ALK-positive non-small cell lung cancer
Targeting genomic alterations, such as epidermal growth factor receptor
(EGFR) mutations and anaplastic lymphoma kinase (ALK) gene
rearrangements, have radically changed the treatment of patients with
non-small cell lung cancer (NSCLC). In the case of ALK-rearranged gene,
subsequent rapid development of effective genotype-directed therapies
with ALK tyrosine kinase inhibitors (TKIs) triggered major advances in
the personalized molecularly based approach of NSCLC. Crizotinib was the
first-in-class ALK TKI with proven superiority over standard
platinum-based chemotherapy for the 1st-line therapy of ALK-rearranged
NSCLC patients. However, the acquired resistance to crizotinib and its
diminished efficacy to the central nervous system (CNS) relapse led to
the development of several novel ALK inhibitors, more potent and with
different selectivity compared to crizotinib. To date, four ALK TKIs,
crizotinib, ceritinib, alectinib and brigatinib have received approval
from the Food and Drug Administration (FDA) and/or the European
Medicines Agency (EMA) and even more agents are currently under
investigation for the treatment of ALK-rearranged NSCLC. However, the
optimal frontline approach and the exact sequence of ALK inhibitors are
still under consideration. Recently announced results of phase III
trials recognized higher efficacy of alectinib compared to crizotinib in
first-line setting, even in patients with CNS involvement. In this
review, we will discuss the current knowledge regarding the biology of
the ALK-positive NSCLC, the available therapeutic inhibitors and we will
focus on the raised issues from their use in clinical practise
Treating ALK-positive non-small cell lung cancer
Targeting genomic alterations, such as epidermal growth factor receptor
(EGFR) mutations and anaplastic lymphoma kinase (ALK) gene
rearrangements, have radically changed the treatment of patients with
non-small cell lung cancer (NSCLC). In the case of ALK-rearranged gene,
subsequent rapid development of effective genotype-directed therapies
with ALK tyrosine kinase inhibitors (TKIs) triggered major advances in
the personalized molecularly based approach of NSCLC. Crizotinib was the
first-in-class ALK TKI with proven superiority over standard
platinum-based chemotherapy for the 1st-line therapy of ALK-rearranged
NSCLC patients. However, the acquired resistance to crizotinib and its
diminished efficacy to the central nervous system (CNS) relapse led to
the development of several novel ALK inhibitors, more potent and with
different selectivity compared to crizotinib. To date, four ALK TKIs,
crizotinib, ceritinib, alectinib and brigatinib have received approval
from the Food and Drug Administration (FDA) and/or the European
Medicines Agency (EMA) and even more agents are currently under
investigation for the treatment of ALK-rearranged NSCLC. However, the
optimal frontline approach and the exact sequence of ALK inhibitors are
still under consideration. Recently announced results of phase III
trials recognized higher efficacy of alectinib compared to crizotinib in
first-line setting, even in patients with CNS involvement. In this
review, we will discuss the current knowledge regarding the biology of
the ALK-positive NSCLC, the available therapeutic inhibitors and we will
focus on the raised issues from their use in clinical practise
Lymphocytic infiltration and Chemotherapy Response Score as prognostic markers in ovarian cancer patients treated with Neoadjuvant chemotherapy
Neoadjuvant Chemotherapy (NACT) followed by Interval Debulking Surgery (IDS) is an accepted frontline treatment in patients with advanced Epithelial Ovarian Cancer (EOC). Histopathologic assessment of tumor post NACT may provide a surrogate for response to treatment. The present study aims to characterize the pathological response and to examine its prognostic significance in these patients. Medical records of women with EOC treated in our institution from 2011 to 2016 were retrospectively identified. IDS specimens were reviewed by study pathologist and Chemotherapy Response Score (CRS), lymphocytic infiltration, necrosis and mitosis were assessed. 55 patients with EOC treated with NACT were identified and 48 had complete clinical and pathological data. Median age was 63 years. CRS assessed at omentum predicted PFS when adjusted for age, stage, debulking status (complete, optimal, suboptimal) and post IDS bevacizumab administration (mPFS CRS 1 vs 2 vs 3: 10.3–14–18.7 months 95% CI [7.4–15.7], [12.2–22.9], [13.5–31.3]). Presence of lymphocytic infiltration was associated with improved OS (log-rank test P = 0.015). Post IDS bevacizumab was associated with shorter PFS in patients with lymphocytic infiltration. BRCA status was known for 25 patients and presence of BRCA1/2 mutations was strongly correlated with lymphocytic infiltration (P = 0.011) but not CRS omentum (P = 0.926). Our study confirms the predictive value of CRS in EOC patients treated with NACT and IDS, but also demonstrates the prognostic significance of lymphocytic infiltration as well as its possible interaction with bevacizumab treatment. © 2020 Elsevier Inc