Treatment outcomes and prognostic factors in patients with driver mutant non-small cell lung cancer and de novo brain metastases.

Central nervous system (CNS) metastases can be seen at a rate of 30% in advanced stages for patients with non-small cell lung cancer (NSCLC). Growing evidence indicates the predictive roles of driver gene mutations in the development of brain metastases (BM) in recent years, meaning that oncogene-driven NSCLC have a high incidence of BM at diagnosis. Today, 3rd generation targeted drugs with high intracranial efficacy, which can cross the blood-brain barrier, have made a positive contribution to survival for these patients with an increased propensity to BM. It is important to update the clinical and pathological factors reflected in the survival with real-life data. A multi-center, retrospective database of 306 patients diagnosed with driver mutant NSCLC and initially presented with BM between between November 2008 and September 2022 were analyzed. The median progression-free survival (mPFS) was 12.25 months (95% CI, 10-14.5). While 254 of the patients received tyrosine kinase inhibitor (TKI), 51 patients received chemotherapy as first line treatment. The median intracranial PFS (iPFS) was 18.5 months (95% CI, 14.8-22.2). The median overall survival (OS) was 29 months (95% CI, 25.2-33.0). It was found that having 3 or less BM and absence of extracranial metastases were significantly associated with better mOS and iPFS. The relationship between the size of BM and survival was found to be non-significant. Among patients with advanced NSCLC with de novo BM carrying a driver mutation, long-term progression-free and overall survival can be achieved with the advent of targeted agents with high CNS efficacy with more conservative and localized radiotherapy modalities.

Liver toxicity with ribociclib in a patient with metastatic hormone receptor positive postmenopausal breast cancer.

INTRODUCTION: In recent years, highly selective reversible CDK4/6 inhibitors have been combined with aromatase inhibitors for their efficacy and ease of application in the treatment of advanced stage of hormone-responsive breast cancers. Oral use of these drugs facilitates patient compliance. However, adverse drug reactions are reported due to these drugs, in the literature. Diverse adverse reactions such as skin reactions, liver toxicity, and vitiligo with ribociclib have been reported. CASE REPORT: In this study, we present of liver toxicity due to the use of ribociclib in a case of advanced breast cancer with metastases. It is noteworthy that the patient did not have any other concomitant disease and did not take any other medication. MANAGEMENT AND OUTCOME: After the 600 mg initial dose of ribociclib, neutropenia occurred at the beginning of the therapy, the dose was reduced to 400 mg, and liver enzymes started to rise in the second month of the therapy. In the fifth month of the intermittent treatment period, liver toxicity was grade 3. DISCUSSION: Liver adverse reaction occurred due to ribociclib use in the patient who had no history of any other disease. The Naranjo algorithm score was evaluated as 9. Considering the excretion of ribociclib by sulfation, cysteine conjugation, and glucuronidation, which are phase II reactions, n-acetyl cysteine (NAC) treatment (600 mg/day) was started for the patient. NAC therapy is recommended to reduce elevated liver enzymes in the case. The patient's treatment has been continuing with palbociclib for 5 months. No increase in liver enzymes was observed.

Prognosis-related novel immunostaining pattern for programmed cell death ligand 1 and prognostic value of tumour-infiltrating lymphocytes in triple-negative breast cancer.

This study aims to determine the prognostic significance of programmed cell death ligand 1 (PD-L1) expression and tumour-infiltrating lymphocytes (TILs) in triple- negative breast cancer (TNBC). PD-L1 expression and TIL percentage were determined in TNBCs that did not receive neoadjuvant therapy. The relationship between PD-L1 expression and the percentage of TILs with survival was investigated. The presence of intratumoural PD-L1-positive tumour-infiltrating immune cells (TIICs) in tumours with ≥ 1% PD-L1 expression was identified as a new PD-L1 evaluation parameter. The presence of intratumoural PD-L1-positive TIICs as a new parameter in PD-L1-positive cases increased overall survival. The percentage of TILs increased in both overall and distant metastasis-free survival (p = 0.040 and p = 0.006, respectively). As a result, it was found that the risk of death was increased 5.18-fold (p = 0.013) in patients without intratumoural PD-L1-positive TIICs. This risk of death was calculated to be 5.40-fold higher in patients with TIL percentage ≤ 10% than in those with > 40% (p = 0.024), and the risk of distant metastasis was calculated to be 11.95 times higher. In our study, we discovered that the percentage of TILs made a statistically significant difference in TNBC survival. The presence of intratumoural PD-L1-positive TIICs in PD-L1-positive cases significantly increased survival.

Comparison of Alectinib/Crizotinib Data in First-Line Therapy in Patients with Anaplastic LymphomakinasePositive Nonsmall Cell Lung Carcinoma with Poor Prognostic Features for Alectinib.

OBJECTIVE: Alectinib has a much better central nervous system transmission than crizotinib in patients diagnosed with anaplastic lymphoma kinase mutation-positive nonsmall cell lung carcinoma. We aimed to investigate alectinib's efficacy in the treatment and its place in the first-line treatment and report our real-life data. MATERIAL AND METHODS: The data of 38 patients who were diagnosed with anaplastic lymphoma kinase-positive nonsmall cell lung carcinoma in our clinic between 2016 and 2021, who did not receive any treatment before were retrospectively analyzed. RESULTS: Of the 19 patients who received alectinib, 14 had multiple, and 6 had pretreatment brain metastases. No newly emerging brain metastases were detected during the treatment period. The progression-free survival of patients was 23.5 ± 4.2 months, and overall survival was 24.6 ± 4.1 months. Progression was observed in 10 (52.6%) patients. Of the 19 patients who received crizotinib, 7 had multiple metastases, and brain metastases were detected in 1 patient before treatment and 6 patients during the treatment period. Progression-free survival of crizotinib patients was 17.1 ± 4.8 months and their overall survival was 26.5 ± 6.1 months. Progression was observed in 17 (89.5%) patients. The second line of alectinib could be given to 8 of these patients. Overall survival after second-line treatment of alectinib was 18.2 ± 7.0 months. Overall survival of the patients who could not receive second-line treatment of alectinib was 4.0 ± 2.0 months. CONCLUSION: The progression rate was lower in alectinib than the crizotinib patients, although there were more patients with multiple metastases and brain metastases in the alectinib arm.

Is there any prognostic significance in pleural involvement and/or effusion in patients with ALK-positive NSCLC?

PURPOSE: Anaplastic lymphoma kinase (ALK) mutations occurs in approximately 3-5% of patients with non-small cell lung cancer (NSCLC). Pleural involvement/effusion is common in ALK-positive patients with NSCLC at baseline. The aim of the study was to evaluate the characteristics of ALK-positive patients who have Ple-I/E. METHODS: In this multicenter study, patients with ALK-positive NSCLC who have Ple-I/E were retrospectively analyzed. Clinical and demographic characteristics of the disease, response rates, median progression-free survival (PFS), and overall survival (OS) were evaluated in 362 ALK-positive patients with NSCLC. RESULTS: Of the patients, 198 (54.7%) were male. The median age at the time of diagnosis was 54 (range 21-85) years. All patients' histology was adenocarcinoma (100%). At baseline, 57 (15.7%) patients had Ple-I/E. There was no association between Ple-I/E and gender, lung metastasis, or distant lymphadenopathy (LAP) metastasis. The frequencies of liver, brain, and bone metastases were significantly higher in ALK-positive patients without Ple-I/E compared to those with Ple-I/E (respectively 18.2% vs 4.8%, p = 0.008; 19.1% vs 4.8%, p = 0.001; 20.6% vs 8.9%, p = 0.002). The median PFS was longer in ALK-positive patients who had Ple-I/E (18.7 vs 10.6 months, p = 0.017). Similarly, the median OS was longer in ALK-positive patients who had Ple-I/E (44.6 vs 22.6 months, p = 0.051). CONCLUSION: Brain, liver, and bone metastases were lower in ALK-positive patients with Ple-I/E. Patients presented with Ple-I/E were prone to have better PFS and OS.

Real-life comparison of afatinib and erlotinib in non-small cell lung cancer with rare EGFR exon 18 and exon 20 mutations: a Turkish Oncology Group (TOG) study.

OBJECTIVES: To compare the survival of first- and second-generation tyrosine kinase inhibitors (TKIs) in patients with rare EGFR exon 18 and exon 20 mutation-positive non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: We retrospectively evaluated survival characteristics of 125 patients with EGFR exon 18 and exon 20 mutated NSCLC who received erlotinib or afatinib as first line treatment between 2012 and 2021 from 34 oncology centres. Since exon 20 insertion is associated with TKI resistance, these 18 patients were excluded from the study. RESULTS: EGFR exon 18 mutations were seen in 60%, exon 20 mutations in 16%, and complex mutations in 24% of the patients with NSCLC who were evaluated for the study. There were 75 patients in erlotinib treated arm and 50 patients in afatinib arm. Patients treated with erlotinib had progression-free survival time (PFS) of 8.0 months and PFS was 7.0 months in the afatinib arm (p = 0.869), while overall survival time (OS) was 20.0 vs 24.8 months, respectively (p = 0.190). PFS of exon 18 mutated arm was 7.0 months, exon 20 mutated arm was 4.3 months, and complex mutation positive group was 17.3 months, and this was statistically significant (p = 0.036). The longest OS was 32.5 months, seen in the complex mutations group, which was not statistically different than exon 18 and in exon 20 mutated groups (21.0 and 21.2 months, respectively) (p = 0.323). CONCLUSION: In this patient group, especially patients with complex mutations are as sensitive to EGFR TKI treatment similar to classical mutations, and in patients with rare exon 18 and exon 20 EGFR mutation both first- and second-generation EGFR-TKIs should be considered, especially as first- and second-line options.

Avascular necrosis during alectinib treatment: Case report.

CASE REPORT: We present our patient who used alectinib due to anaplastic lymphoma kinase positivity and developed avascular necrosis in the femoral head. MANAGEMENT AND OUTCOME: In our patient who had been taking alectinib for a long time due to anaplastic lymphoma kinase positivity, avascular necrosis of the femoral head was detected as a result of the examination performed due to hip pain. Due to the responsibility of the disease, her treatment continued by making profit and loss account. DISCUSSION: Femoral head avascular necrosis can be seen with tyrosine kinase inhibitors, although it is very rare. This is the case in the literature to develop avascular necrosis due to alectinib. We think that femoral head necrosis may develop in the patient group using alectinib and care should be taken in this regard.

Prognostic and predictive role of liquid biopsy in lung cancer patients.

Introduction: Lung cancer (LC) is a leading cause of cancer-related mortality worldwide. Approximately 80% of LC cases are of the non-small cell lung cancer (NSCLC) type, and approximately two-thirds of these cases are diagnosed in advanced stages. Only systemic treatment methods can be applied to patients in the advanced stages when there is no chance of surgical treatment. Identification of mutations that cause LC is of vital importance in determining appropriate treatment methods. New noninvasive methods are needed to repeat and monitor these molecular analyses. In this regard, liquid biopsy (LB) is the most promising method. This study aimed to determine the effectiveness of LB in detecting EGFR executive gene mutations that cause LC. Methods: One hundred forty-six patients in stages IIIB and IV diagnosed with non-squamous cell non-small cell LC were included. Liquid biopsy was performed as a routine procedure in cases where no mutation was detected in solid tissue or in cases with progression after targeted therapy. Liquid biopsy samples were also obtained for the second time from 10 patients who showed progression under the applied treatment. Mutation analyses were performed using the Cobas® EGFR Test, a real-time PCR test designed to detect mutations in exons 18, 20, and 21 and changes in exon 19 of the EGFR gene. Results: Mutation positivity in paraffin blocks was 21.9%, whereas it was 32.2% in LB. Solids and LB were compatible in 16 patients. Additionally, while no mutation was found in solid tissue in the evaluation of 27 cases, it was detected in LB. It has been observed that new mutations can be detected not only at the time of diagnosis, but also in LB samples taken during the follow-up period, leading to the determination of targeted therapy. Discussion: The results showed that "liquid biopsy" is a successful and alternative non-invasive method for detecting cancer-causing executive mutations, given the limitations of conventional biopsies.

Crizotinib efficacy and safety in patients with advanced NSCLC harboring MET alterations: A real-life data of Turkish Oncology Group.

Crizotinib is a multikinase inhibitor, effective in non-small cell lung cancer (NSCLC) harboring mesenchymal-epidermal transition (MET) alterations. Although small prospective studies showed efficacy and safety of crizotinib in NSCLC with MET alterations, there is limited real-life data. Aim of this study is to investigate real-life efficacy and safety of crizotinib in patients with advanced NSCLC harboring MET alterations. This was a retrospective, multicenter (17 centers) study of Turkish Oncology Group. Patients' demographic, histological data, treatment, response rates, survival outcomes, and toxicity data were collected. Outcomes were presented for the study population and compared between MET alteration types. Total of 62 patients were included with a median age of 58.5 (range, 26-78). Major histological type was adenocarcinoma, and 3 patients (4.8%) had sarcomatoid component. The most common MET analyzing method was next generation sequencing (90.3%). MET amplification and mutation frequencies were 53.2% (n = 33) and 46.8% (n = 29), respectively. Overall response rate and disease control rate were 56.5% and 74.2% in whole study population, respectively. Median progression free survival (PFS) was 7.2 months (95% confidence interval [CI]: 3.8-10.5), and median overall survival (OS) was 18.7 months (95% CI: 13.7-23.7), regardless of treatment line. Median PFS was 6.1 months (95% CI: 5.6-6.4) for patients with MET amplification, whereas 14.3 months (95% CI: 6.7-21.7) for patients with MET mutation (P = .217). Median PFS was significantly longer in patients who have never smoked (P = .040), have good performance score (P < .001), and responded to the treatment (P < .001). OS was significantly longer in patients with MET mutation (25.6 months, 95% CI: 15.9-35.3) compared to the patients with MET amplification (11.0 months; 95% CI: 5.2-16.8) (P = .049). In never-smokers, median OS was longer than smoker patients (25.6 months [95% CI: 11.8-39.3] vs 16.5 months [95% CI: 9.3-23.6]; P = .049). The most common adverse effects were fatigue (50%), peripheral edema (21%), nausea (29%) and diarrhea (19.4%). Grade 3 or 4 adverse effects were observed in 6.5% of the patients. This real-life data confirms efficacy and safety of crizotinib in the treatment of advanced NSCLC harboring MET alteration.

Systemic Immune Inflammation Index as a Key Marker of Survival and Immune-related Adverse Events in Immune Checkpoint Inhibitor Therapy.

OBJECTIVE: To evaluate the prognostic significance of the new index designed by formulating neutrophil, lymphocyte, and platelet counts in patients with metastatic disease receiving immune checkpoint inhibitors (ICI) and its effect on the immune-related adverse events (irAEs). STUDY DESIGN: Cohort study. PLACE AND DURATION OF STUDY: Department of Medical Oncology, University of Manisa Celal Bayar, University of Aydin Adnan Menderes, and University of Ege, and Izmir Kent Hospital, Turkey, from January 2016 to April 2020. METHODOLOGY: Patients with metastatic disease receiving ICI sufficient follow-up data were included. Patients, who had received treatment for a minimum of 3 months, were evaluated for the response. Systemic immune-inflammation index (SII) was calculated as neutrophil (/L) × (lymphocyte (/L) / platelet (/L). The cut-off value was determined by examining the area under the receiver operating characteristic (ROC) curve for the SII value. The endpoints of this study included overall survival (OS) and progression-free survival (PFS). RESULTS: A total of 168, patients who received ICI in the metastatic stage, were evaluated. The OS of the patients with low SII scores was 110.8 months (95% CI, 88.2-133.5), while patients with high SII scores were 36.0 months (95% CI, 28.4-43.6) and reached statistical significance (p <0.001). The results of univariate (HR=3.376, 95% CI, 1.986-5.739, p<0.001 and multivariate (HR=2.792, 95% CI, 1.495-5.215, p=0.011) analyses were statistically significant as well. CONCLUSION: The SII score in patients with metastatic disease receiving ICI was closely related to the prognosis. Patients with a high SII score are associated with a worse prognosis, these patients develop fewer irAEs. KEY WORDS: Systemic immune inflammation index, Overall survival, Progression-free survival, Immune checkpoint inhibitor, Pembrolizumab, Nivolumab.

Evaluation of Treatment Efficacy of Tyrosine Kinase Inhibitors in Rare Single EGFR Exon 21 L861Q Mutation: Single Center Experience.

OBJECTIVE: Epidermal growth factor receptor mutations are the second most common oncogenic driver event in non-small cell lung cancer. We aimed to compare the first generation erlotinib treatment with the second generation afatinib treatment in patients with non- small cell lung cancer with epidermal growth factor receptor exon 21 L861Q mutation. MATERIAL AND METHODS: Progression-free survival and overall survival of 30 non-small cell lung cancer patients treated with erlo- tinib or afatinib due to single epidermal growth factor receptor L861Q positivity were compared retrospectively. The number of patients included in the first, second, and third treatment line was 15 (50.0%), 11 (36.7%), and 4 (13.3%), respectively. RESULTS: There were 23 patients in the erlotinib arm and 7 patients in the afatinib arm. Median progression-free survival was 12.8 months in the erlotinib group and 9.3 months in the afatinib group. Median overall survival in erlotinib and afatinib groups was 77.9 months and 30.3 months, respectively. No statistically significant difference was found in the comparison of these survival times. CONCLUSION: Survival times of erlotinib and afatinib treatment are similar in patients with a single epidermal growth factor receptor L861Q mutation. In patients receiving tyrosine kinase inhibitors treatment, the female gender has a positive effect on progression-free survival, and being a non-smoker has a positive effect on overall survival. In patients with rare mutation exon 21 L861Q positivity, both first-generation and second-generation tyrosine kinase inhibitors should be considered.

The effectiveness and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early-stage human epidermal growth factor receptor 2-positive breast cancer: Turkish Oncology Group study.

In our study, we aimed to evaluate the pathological response rates and side effect profile of adding pertuzumab to the treatment of HER2+ locally advanced, inflammatory, or early-stage breast cancer. This study was conducted by the Turkish Oncology Group (TOG) with data collected from 32 centers. Our study was multicentric, and a total of 364 patients were included. The median age of the patients was 49 years (18-85 years). Two hundred fifteen (60%) of the cases were hormone receptor/HER2+ positive(ER+ or PR+, or both), and 149 (40%) of them were HER2-rich (ER and PR negative). The number of complete responses was 124 (54%) in the docetaxel+trastuzumab+pertuzumab arm and 102 (45%) in the paclitaxel+trastuzumab+pertuzumab arm, and there was no difference between the groups in terms of complete response. In 226 (62%) patients with complete response, a significant correlation was found with DCIS, tumor focality, removed lymph node, and ER status P < 0.05. Anemia, nausea, vomiting, myalgia, alopecia, and mucosal inflammation were significantly higher in the docetaxel arm, P < 0.05. In our study, no statistical difference was found between the before-after echocardiography values. DCIS positivity in biopsy before neoadjuvant chemotherapy, tumor focality; the number of lymph nodes removed and ER status were found to be associated with pCR. In conclusion, we think that studies evaluating pCR-related clinicopathological variables and radiological imaging features will play a critical role in the development of nonsurgical treatment approaches.

PDL-1 Expression and Survival in Metastatic Non-small Cell Lung Cancer Patients Who Received Chemotherapy as First-Line Treatment.

OBJECTIVE: To show the effect of programmed cell death protein-1ligand (PDL-1) level on survival times in patients with metastatic non-small cell lung cancer (mNSCLC) receiving chemotherapy, to determine the relationship between PDL-1 level, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). MATERIAL AND METHODS: The data of 158 patients who received chemotherapy for mNSCLC were evaluated retrospectively. Clinical and demographic data, PDL-1 expression levels and follow-up periods of the patients were recorded. The patients were divided into 2 groups according to PDL-1 levels. RESULTS: In all patients, progression free survival (PFS) was 5.6 months and overall survival (OS) was 18.8 months. Patients with low PDL-1 had a longer PFS than patients with high PDL-1 (p:0.038). In the gemcitabine and taxane groups, patients with low PDL-1 had a longer PFS than patients with high PDL-1 (p:0.047). There was a significant correlation between NLR and PDL-1 levels. In the groups with high PDL-1, patients with low NLR levels had higher OS than patients with high NLR level (p:0.043). Also, there was a significant difference between the OS patients with low and high PLR levels (p:0.520). CONCLUSION: In patients with mNSCLC whose PDL-1 levels and NLR levels are low, immunogenic chemotherapies such as gemcitabine and taxane can be tried as an alternative treatment.

Ado-trastuzumab emtansine associated spider telangiectasia.

INTRODUCTION: Breast cancer is the most common cancer in women. Human epidermal growth factor receptor 2 (HER2) positivity rate is 20% and generally has a poor prognosis. Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate consisting of HER2 target monoclonal antibody trastuzumab and microtubule inhibitor emtansine. The most common side effects are fatigue, diarrhea, anemia, and it is generally a safe and tolerable agent. CASE REPORT: In our case, we reported our patient who developed mucosal and cutaneous telangiectasia after T-DM1 treatment and who had a complete response in metastases after skin lesions. MANAGEMENT AND OUTCOME: While no side effects were observed during the use of T-DM1 for HER2 positive disease, nose bleeding and spider telangiectasia on the skin developed in the 9th month of the treatment. In these lesions, which did not require any treatment, no regression was observed during T-DM1 treatment. DISCUSSION: We think that T-DM1, which was detected with a low incidence of skin toxicity in studies, may form telangiectatic lesions due to vascular dilatation through emtansine, and therefore care should be taken in the treatment of T-DM1.

Predictive role of neutropenia under crizotinib treatment in ALK-rearranged nonsmall cell lung cancer patients: A single-institution retrospective analysis.

Background: Anaplastic lymphoma kinase (ALK)-rearranged nonsmall cell lung cancer (NSCLC) represents a molecular subgroup with high sensitivity to ALK inhibitors. Tyrosine kinase inhibitor crizotinib, an anticancer drug acting as an ALK inhibitor, has shown remarkable response in ALK-positive NSCLC. The aim of our study is to explore the adverse events (AEs) of patients on crizotinib therapy and analyze the predictability of AEs for better survival or response on NSCLC patients. Methods: The medical records of our ALK-positive metastatic NSCLC patients who applied between years 2013 and 2018 had been reviewed retrospectively. ALK positivity of all patients had been detected by fluorescence in situ hybridization and no other driver mutations were present. Patient demographics, performance status, smoking history, previous treatments, metastatic sites, and AEs were recorded for further analyses. Results: Thirty-six ALK-positive metastatic NSCLC patients were included in the study. Median follow-up was 30.1 months. Median progression-free survival (PFS) for patients who developed hepatic, cardiac, or endocrine toxicities was similar when compared to patients who did not develop. Although there was a numeric median PFS difference between patients who did develop visual disorders (18.4 months) and did not develop visual disorders (15.5 month), this was not regarded as statistically significant. However, median PFS of the patients who developed neutropenia upon crizotinib treatment (31.9 months) was found to be more favorable than the patients with normal neutrophil counts (12.8 months) (P = 0.026). Conclusion: Neutropenia under crizotinib treatment was found to be associated with improved PFS suggesting that neutropenia might be an important determinant in treatment and survival strategies.

Re-use of erlotinib in a patient using osimertinib after erlotinib, case report.

INTRODUCTION: Most patients with non-small-cell lung cancer tumors that have epidermal growth factor receptor (EGFR) mutations have deletion mutations in exon 19 or exon 21, or both.In recent years, targeted therapies in lung cancer have increased survival, but the development of resistance to these drugs poses a major problem. Thesubstitution of methionineforthreonine at position 790 (T790M) mutation,is primarily responsible for this resistance. However, after osimertinib used in T790M positivepatients treatment options are generally limited to chemotherapy. CASE REPORT: We reported the efficacy of erlotinib, which we reapplied due to the disappearance of the resistance mutation after osimertinib in a 68-year-old patient using osimertinib after erlotinib.Management and outcome: In the patient using erlotinib due to exon 19 deletion when progression was observed and T790M positivity was detected, osimertinib treatment was initiated. However, when T790M was found to be negative with rebiopsy in progression after osimertinib, a complete response was achieved by restarting erlotinib. DISCUSSION: The strategy of restarting erlotinib treatment with negative T790M mutation detected in biopsies of patients with osimertinib resistance may be an acceptable treatment option.

The effectiveness of cetuximab and panitumumab when combined with FOLFIRI in second-line treatment of KRAS wild type metastatic colorectal cancers. Single centre experience.

Panitumumab and cetuximab are monoclonal antibodies known to be effective in metastatic colorectal cancer (mCRC). Although the survival benefits when combined with chemotherapy have been determined, there are no studies comparing the two agents with chemotherapy in the second-line treatment. In this study, we aimed to compare the efficacy of cetuximab vs panitumumab in patients who previously received chemotherapy. Who progressed after first-line treatment for K-ras wild type mCRC were analyzed. The efficacy of cetuximab vs panitumumab on overall survival (OS) and progression-free survival (PFS) when combined with FOLFIRI regimen was compared retrospectively. Median PFS was 6.9 months in the cetuximab group and 4.7 months in the panitumumab group. Median OS cetuximab and panitumumab groups were 18.4 and 12.2 months, respectively. In the second-line treatment of K-ras wild type mCRC, both PFS and OS were found to be longer in patients receiving cetuximab than in patients receiving panitumumab, but no statistically significant difference was found.

Combination of zoledronic acid and serine/threonine phosphatase inhibitors induces synergistic cytotoxicity and apoptosis in human breast cancer cells via inhibition of PI3K/Akt pathway.

The aim of this study was to investigate the cytotoxic and apoptotic effects of zoledronic acid (ZA) in combination with serine/threonine protein phosphatase inhibitors, calyculin-A (CA) and okadaic acid (OA), in human MCF-7 and MDA-MB-231 breast cancer cells. XTT cell viability assay was used to evaluate cytotoxicity. DNA fragmentation and caspase-3/7 activity assays were performed to evaluate apoptosis. Activities of phosphatase 1 (PP1) and phosphatase 2A (PP2A) were measured by serine/threonine phosphatase ELISA kit. Expression levels of PI3K, p-PI3K, Akt, p-Akt, Bcl-2, p-Bcl-2, Bad, and p-Bad proteins were evaluated by Western blot analysis. Combination of ZA with either CA or OA showed synergistic cytotoxicity and apoptosis as compared to any agent alone in both MCF-7 and MDA-MB-231 breast cancer cells. Combination treatment also resulted in inhibition of both PP1 and PP2A activities. Both agents used alone or in combination did not induce significant changes in total PI3K, Akt, Bcl-2, and Bad expressions, while p-PI3K, p-Akt, p-Bcl-2, and p-Bad levels were reduced by the combination treatment as compared to agents alone. Moreover, apoptotic effect of combination treatment was significantly inhibited in the presence of LY294002, a specific PI3K inhibitor, in both breast cancer cell lines. In conclusion, synergistic apoptotic effect of the combination treatment is correlated with the block of the PI3K/Akt signal pathway in breast cancer cells.