Vaccine third dose and cancer patients: necessity or luxury?

The current state of the SARS-CoV-2 pandemic is an equilibrium between expanding vaccine coverage on the one hand, and emergence of variants of concern which compromise vaccine effectiveness and enhance viral transmission on the other. Inequity in vaccine distribution, primarily an ethical issue, challenges this equilibrium, as industrialized countries prepare to administer a third booster dose to their population. Solid tumor cancer patients typically respond well to initial full vaccination and someone could argue that they should not be prioritized for an adjuvant third dose, since protection from severe disease has largely been achieved with the two-dose regimen. Nevertheless, their immune status is dynamic and not all of them exhibit an adequate immune response. A booster third dose is necessary for the inadequate responders, while it will result in better protection of all patients from mild disease as well, which if presented could have ominous consequences due to their overall frailty, and their need to adhere to strict therapeutic schemes. International scientific and public health communities should develop approaches that allow for wide immediate vaccination coverage of the developing world, in parallel with administration of adjuvant doses to solid tumor cancer patients (and other at-risk categories) of the developed nations, in order to avoid prolonging the pandemic, which will be prospectively against cancer patients' best interest.

ABREAST: a prospective, real-world study on the effect of nab-paclitaxel treatment on clinical outcomes and quality of life of patients with metastatic breast cancer.

PURPOSE: The efficacy of nab-paclitaxel in patients with metastatic breast cancer (MBC) has been demonstrated in randomized clinical trials. However, real-world evidence on effectiveness remains limited. PATIENTS AND METHODS: The primary objective of this multicenter prospective study was to assess the overall response rate (ORR) of patients with MBC treated with nab-paclitaxel. Secondary objectives included progression-free survival (PFS), overall survival (OS) and quality of life, assessed with the Functional Assessment of Cancer Therapy-Breast (FACT-B) instrument. RESULTS: Eligible patients (N = 150; 36% with de novo MBC presentation) with a median age of 64.5 years were enrolled (86% were ER+, 33.3% (50/150) were ≥ 70 years of age and 53% were treated in the third or later line of treatment). A median of 6 cycles were administered but 26% of patients required dose reduction due to toxicity. The ORR was 26.7% [95% confidence interval (CI) 19.6-33.7], the median PFS was 6.2 months (95% CI 5.2-7.3), and the median OS 21.1 months (95% CI 17.2-not estimable). There was no statistical significant difference in the median PFS of patients < and ≥ 70 years of age. The patients' baseline FACT-B total score remained unchanged. The serious and non-serious adverse event incidence rates were 13% and 48%, respectively. CONCLUSIONS: This prospective study provides further evidence on quality of life, efficacy, and safety of nab-paclitaxel in patients with MBC and sheds more light in special subpopulations such as the elderly and those treated beyond the second line.

Three- versus six-month adjuvant FOLFOX or CAPOX for high-risk stage II and stage III colon cancer patients: the efficacy results of Hellenic Oncology Research Group (HORG) participation to the International Duration Evaluation of Adjuvant Chemotherapy (IDEA) project.

BACKGROUND: The International Duration Evaluation of Adjuvant Chemotherapy (IDEA) aimed to investigate whether a 3 months (3M) of oxaliplatin/fluoropyrimidine-based adjuvant chemotherapy (CT) is non-inferior to the 6-month (6M) administration in 3-year disease-free survival (3yDFS) in high-risk (HR) stage II or stage III colon cancer (CC). METHODS: Hellenic Oncology Research Group (HORG)-IDEA randomized patients between 3M and 6M of CT with FOLFOX4 or CAPOX. RESULTS: In total 1115 patients, 413 with HR stage II and 702 with stage III CC, were randomized. The median follow-up was 67.0 (38.3-126.0) months. Overall, 394 DFS events (202 in 3M arm and 192 in 6M arm) where recorded. The 3yDFS rate was 77.2% [95% confidence interval (CI) 72.1% to 82.3%] for 3M and 77.9% (72.6% to 82.5%) for 6M of treatment [hazard ratio (HR) 1.05 (95% CI 0.61-1.55); P = 0.647]. Eighty DFS events (3M N = 41; 6M N = 39) were observed in HR stage II patients for a 3yDFS rate of 82.7% and 83.4%, respectively (HR 1.05; 95% CI 0.68-1.63, P = 0.829). For stage III patients, 314 DFS events (3M N = 161 and 6M N = 153) were observed, for a 3yDFS rate of 72.9% for 3M versus 74.1% for 6M (HR 1.06; 95% CI 0.81-1.42, P = 0.622). For HR stage II patients receiving FOLFOX4, 3yDFS rate was 76.7% for 3M and 79.3% for 6M (HR 1.21; 95% CI 0.54-2.70). For HR stage II patients receiving CAPOX the 3yDFS rate was 85.4% for 3M and 83.8% for 6M (HR 0.99; 95% CI 0.59-1.67). For stage III patients receiving FOLFOX4, the 3yDFS rate was 71.5% for 3M and 77.3% for 6M (HR 1.18; 95% CI 0.74-1.86). For stage III patients receiving CAPOX, the 3yDFS rate was 74.5% for 3M and 74.7% for 6M (HR 0.99; 95% CI 0.70-1.44). CONCLUSIONS: The results of the HORG-IDEA study are in line with those of the global IDEA project, indicating that the 3yDFS is dependent on the administered adjuvant regimen and the choice and duration of regimen should be personalized. CLINICALTRIALS.GOV REGISTRATION NUMBER: NCT01308086.

Efficacy and tolerance of frontline bevacizumab-based chemotherapy for advanced non-small cell lung cancer patients: a multicenter, phase IV study of the Hellenic Oncology Research Group (HORG).

INTRODUCTION: The addition of bevacizumab to the first-line chemotherapy of advanced non-small cell lung cancer (NSCLC) of non-squamous histology has been shown to improve survival. A multicenter, single-arm, phase IV study was conducted in order to evaluate the efficacy and toxicity of frontline bevacizumab-based chemotherapy regimens in real life. METHODS: Patients with previously untreated recurrent or metastatic non-squamous, NSCLC, with no contraindications for bevacizumab, were enrolled. Bevacizumab (15 mg/kg every 3 weeks) was administered in combination with both platinum- and non-platinum-based chemotherapy doublets or with single-agent chemotherapy plus bevacizumab. Treatment with bevacizumab was continued until disease progression. The primary end point of the study was the safety profile of bevacizumab regimens, whereas the secondary end points included overall survival, progression-free survival, and overall response rate. RESULTS: From February 2010 to April 2014, a total of 314 patients were enrolled in the study; the median age was 63, 74.8 % were men, 95.9 % had a performance status of 0-1, 90.4 % had metastatic disease, and 94.3 % had adenocarcinoma. Grade ≥3 neutropenia occurred in 11.5 % of the patients, 1.3 % experienced febrile neutropenia, 2.6 % grade ≥3 thrombocytopenia, 2.8 % thromboembolism, and 1.6 % severe bleeding. Treatment discontinuation occurred in 7.0 % of patients because of adverse events. There were three toxic deaths. Median progression-free survival was 7.7 months, and median overall survival was 17.6 months. CONCLUSION: The combination of bevacizumab with chemotherapy in the first-line setting of NSCLC is safe and active when used in appropriately selected patients. CLINICALTRIALS. GOV IDENTIFIER: NCT01934465.

Primary analysis of a prospective, randomized, single-blinded phase II trial evaluating the HER2 peptide AE37 vaccine in breast cancer patients to prevent recurrence.

BACKGROUND: AE37 is the Ii-Key hybrid of the MHC class II peptide, AE36 (HER2 aa:776-790). Phase I studies showed AE37 administered with granulocyte macrophage colony-stimulating factor (GM-CSF) to be safe and highly immunogenic. A prospective, randomized, multicenter phase II adjuvant trial was conducted to evaluate the vaccine's efficacy. METHODS: Clinically disease-free node-positive and high-risk node-negative breast cancer patients with tumors expressing any degree of HER2 [immunohistochemistry (IHC) 1-3+] were enrolled. Patients were randomized to AE37 + GM-CSF versus GM-CSF alone. Toxicity was monitored. Clinical recurrences were documented and disease-free survival (DFS) analyzed. RESULTS: The trial enrolled 298 patients; 153 received AE37 + GM-CSF and 145 received GM-CSF alone. The groups were well matched for clinicopathologic characteristics. Toxicities have been minimal. At the time of the primary analysis, the recurrence rate in the vaccinated group was 12.4% versus 13.8% in the control group [relative risk reduction 12%, HR 0.885, 95% confidence interval (CI) 0.472-1.659, P = 0.70]. The Kaplan-Meier estimated 5-year DFS rate was 80.8% in vaccinated versus 79.5% in control patients. In planned subset analyses of patients with IHC 1+/2+ HER2-expressing tumors, 5-year DFS was 77.2% in vaccinated patients (n = 76) versus 65.7% in control patients (n = 78) (P = 0.21). In patients with triple-negative breast cancer (HER2 IHC 1+/2+ and hormone receptor negative) DFS was 77.7% in vaccinated patients (n = 25) versus 49.0% in control patients (n = 25) (P = 0.12). CONCLUSION: The overall intention-to-treat analysis demonstrates no benefit to vaccination. However, the results confirm that the vaccine is safe and suggest that vaccination may have clinical benefit in patients with low HER2-expressing tumors, specifically TNBC. Further evaluation in a randomized trial enrolling TNBC patients is warranted.

Meta-analysis of the predictive value of KRAS mutations in treatment response using cetuximab in colorectal cancer.

PURPOSE: The monoclonal antibody cetuximab that targets epidermal growth factor receptor (EGFR) has been found effective in the treatment of colorectal cancer. However, mutations in exons 12 and 13 of KRAS oncogene have been reported as negative predictive factors for the treatment response using cetuximab. The purpose of this study was to conduct a meta-analysis of the published studies investigating the predictive value of KRAS mutations in the efficacy of cetuximab in patients suffering from colorectal cancer. METHODS: A systematic search of the literature was performed in PubMed, Medline, and Cochrane databases. Sensitivities, specificities and predictive values (negative and positive) of KRAS mutations as regards treatment response were calculated. RESULTS: Twenty-six studies were initially found during the literature search. After thorough evaluation, 13 papers were excluded for various reasons. Therefore, 13 studies were included in the present meta-analysis. In these studies, specificities were found much higher than sensitivities. Combining the data from the 13 studies, it was found that KRAS mutations comprise a negative predictive biomarker for response to cetuximab with very high specificity (0.96; 95% CI 0.84-0.99), and low sensitivity (0.47; 95% CI 0.43-0.50). Finally, the publication bias was found statistically significant. CONCLUSION: The results of the present meta-analysis suggest that cetuximab should be administered only to patients with colorectal cancer who have the wild type (KRASw) oncogene. Mutations in the KRAS gene are a negative predictive factor for response to cetuximab with very high specificity and low sensitivity. The latter may very well be attributed to additional mechanisms of resistance to anti-EGFR therapies such as mutations in BRAF.

A multicenter randomized phase III trial of vinorelbine/gemcitabine doublet versus capecitabine monotherapy in anthracycline- and taxane-pretreated women with metastatic breast cancer.

BACKGROUND: The Breast Cancer Study Group of the Hellenic Oncology Research Group conducted a phase III trial of single-agent capecitabine versus the vinorelbine/gemcitabine doublet in patients with metastatic breast cancer (MBC) pretreated with anthracyclines and taxanes. The primary objective was to demonstrate superiority of combination treatment in terms of progression-free survival (PFS). PATIENTS AND METHODS: Women with MBC were randomly assigned to receive either capecitabine (Cap arm: 1250 mg/m(2) twice daily, on days 1-14) or vinorelbine/gemcitabine doublet (VG arm: vinorelbine 25 mg/m(2); gemcitabine 1000 mg/m(2); both drugs on days 1 and 15). RESULTS: Seventy-four women were treated on each arm and median PFS was 5.4 versus 5.2 months (P = 0.736), for VG and Cap, respectively. Median overall survival was 20.4 months for the VG arm and 22.4 months for the Cap arm (P = 0.319). Overall response rate was 28.4% in the VG arm and 24.3% in the Cap arm (P = 0.576). Both regimens were generally well tolerated. Neutropenia and fatigue were more common with VG arm and hand-foot syndrome with Cap arm. CONCLUSIONS: This trial failed to demonstrate superiority of vinorelbine/gemcitabine doublet over single-agent capecitabine in terms of PFS. Given the favorable toxicity and convenience of oral administration, single-agent capecitabine is recommended for compliant patients.

Barrett's esophagus: treatment or observation of a major precursor factor of esophageal cancer?

Barrett's esophagus (BE) is a major precursor factor of esophageal cancer (EC). The appropriate management of patients with BE depends on the presence or not of dysplasia and the type of dysplasia that occurs. Due to the small proportion of BE patients that progress to cancer, the value of surveillance programs are a matter of debate. On the contrary, in high risk group of patients surveillance programs have significant impact. Large prospective trials are needed to define the optimal management strategy. Elucidation of carcinogenesis' steps and signal transduction pathways could reveal potential biomarkers in the order of early prediction for a highly malignant neoplasm with dismal prognosis. An efficacious tailored-made manner focusing to the safety profile and associated costs should be practised for less severe disease. In this review a thorough investigation of all available methods dealing with the clinical management of BE is provided.

Randomized phase III trial comparing docetaxel plus epirubicin versus docetaxel plus capecitabine as first-line treatment in women with advanced breast cancer.

BACKGROUND: The purpose of this study was to compare docetaxel plus epirubicin versus docetaxel plus capecitabine combinations as front-line treatment in women with advanced breast cancer (ABC). PATIENTS AND METHODS: Previously untreated patients with ABC were randomly assigned to receive docetaxel 75 mg/m(2) plus epirubicin 75 mg/m(2) (DE) on day 1 or docetaxel 75 mg/m(2) on day 1 plus capecitabine 950 mg/m(2) orally twice daily on days 1-14 (DC) in 21-day cycles. Previous anthracycline-based (neo)-adjuvant chemotherapy was allowed if completed >1 year before enrollment. The primary objective of the study was to compare time to disease progression (TTP). RESULTS: One hundred and thirty-six women were treated on each arm and median TTP was 10.6 versus 11.0 months (P = 0.7), for DE and DC, respectively. According to RECIST criteria we observed 15 (11%) versus 11 (8%) complete responses and 55 (40%) versus 61 (45%) partial responses (P = 0.8), with DE and DC, respectively. Severe toxicity included grade 3-4 neutropenia (57% versus 46%; P = 0.07), febrile neutropenia (11% versus 8%; P = 0.4), hand-foot syndrome (0% versus 4%; P = 0.02), grade 2-3 anemia (20% versus 7%; P = 0.001) and asthenia (12% versus 6%; P = 0.09) with DE and DC, respectively. CONCLUSIONS: The DE and DC regimens have similar efficacy but different toxicity. Either regimen can be used as front-line treatment of ABC.

Leptomeningeal carcinomatosis presenting as bilateral sensorineural deafness and unilateral facial palsy.

This paper describes the case of a 56-year-old man with a history of small cell lung cancer under chemotherapy, who presented with left-sided peripheral facial palsy and progressive bilateral sensorineural deafness due to leptomeningeal carcinomatosis (LMC). Brain magnetic resonance imaging (MRI) of the petrosal bones and posterior cranial fossa revealed 2 solid lesions in the internal acoustic meatuses bilaterally and LMC of the skull base. Whole brain radiation therapy and methotrexate intrathecally were applied to the patient.

Is overcoming hormone resistance in breast cancer possible?

The administration of hormones plays a major role in the treatment of hormone receptor-expressing breast cancers (BCs), both in the adjuvant setting as well as in advanced disease. Hormone-responsive tumors almost uniformly develop resistance, either independently or as a result of exposure to hormones. Overcoming this phenomenon constitutes a perpetual challenge to researchers and clinical oncologists. Understanding the mechanisms leading to hormone resistance is crucial to its inhibition or, at least, its delayed onset. This manuscript provides a brief review of this topic.

Extracellular domain of HER2: a useful marker for the initial workup and follow-up of HER2-positive breast cancer.

PURPOSE: The extracellular domain (ECD) of the HER2 receptor is proposed as a real-time marker of HER2-positive breast cancer (BC). In this study, ECD-HER2 levels were compared with standard clinical and pathological prognostic factors. PATIENTS AND METHODS: In 247 consecutive patients (116 with early or localized BC, 116 with advanced or metastatic BC, and 16 with benign mastopathies), serum ECD-HER2 levels were measured. In 116 advanced-disease patients ECD-HER2 status was also studied by immunohistochemistry (IHC) and compared with established clinical and pathological variables. RESULTS: Mean serum ECD-HER2 value was 19.62 ng/ml (median 10.35, range 3-->250). Mean value in benign mastopathies was 9.04 ng/ml, 9.4 ng/ml in early disease and 34.5 ng/ml in advanced disease. No difference between benign mastopathies and early BC was observed, while significant difference between early and advanced BC (p<0.001) was noted. However, in advanced-disease patients a positive correlation of ECD-HER2 with IHC (p=0.002), disease grade (p=0.034) and level II axillary node involvement (p=0.011) was noted, as well as a significant negative correlation with estrogen receptor (ER) and progesterone receptor (PR) (p=0.035 and p=0.011, respectively). CONCLUSION: ECD-HER2 is a reliable marker for breast cancer, as suggested from the existing literature; therefore, its integration in the initial workup and follow-up routine of breast cancer, particularly the HER2-positive, is proposed.

Modified CAPOX (capecitabine plus oxaliplatin) regimen every two weeks as second-line treatment in patients with advanced colorectal cancer previously treated with irinotecan-based frontline therapy: a multicenter phase II study.

BACKGROUND: To evaluate the efficacy and tolerance of capecitabine (CAP) given every other week and biweekly oxaliplatin (OX; modified CAPOX regimen) in patients with advanced colorectal cancer previously treated with irinote- can-based frontline chemotherapy. METHODS: Sixty-seven patients were enrolled; the median age was 62 years and 62 (92.5%) had a performance status (ECOG) of 0-1. OX and CAP were administered at the dose of 100 mg/m(2) on day 1 and 2,000 mg/m(2) on days 1-7, respectively, every 2 weeks. RESULTS: A total of 429 treatment cycles were administered. Grade 3/4 neutropenia and thrombocytopenia were observed in 4 (6%) and 2 (3%) patients, respectively. Febrile neutropenia complicated 1 treatment cycle. The main nonhematologic toxicities were grade 2/3 peripheral sensory neurotoxicity (10% of patients) and grade 3/4 diarrhea (7%). In an intention-to-treat analysis, 3 (4.5%) complete and 13 (19.4%) partial responses (overall response rate 24%) were observed. Seventeen (24.5%) patients had stable and 27 (40.3%) progressive disease. The median time to tumor progression and overall survival were 5 months and 11.3 months, respectively. CONCLUSIONS: The results indicate that the modified CAPOX regimen is safe and effective as salvage treatment in patients with advanced colorectal cancer who were previously treated with irinotecan-based frontline therapy.

Low-dose capecitabine in breast cancer patients with symptomatic bone marrow infiltration: a case study.

BACKGROUND: The prognosis of patients with metastatic breast cancer and symptomatic bone marrow involvement is poor. The aim of treatment to these patients is palliation. In this study, we sought to determine the efficacy of therapy with low doses of capecitabine in this subgroup of patients. PATIENTS AND METHODS: Five consecutive breast cancer patients with overt bone marrow involvement were treated by low doses of capecitabine in our department. Four out of five patients also received bisphosphonates to palliate skeletal symptoms. The influence of this therapeutic regimen on tumor response, blood count normalization and overall survival was analysed. RESULTS: All patients except one responded in terms of their haematological profile within two months of the initiation of treatment. Duration of haematological response was 8+ months for all patients. In two of them, tumor response in other sites was evaluated as stable disease, in one as partial remission and in one as progressive disease. Two patients survived more than 22 months without bone marrow failure. CONCLUSION: These initial results are very encouraging for this subset of patients with poor prognosis and limited life expectancy. The administration of capecitabine might be an efficient alternative treatment option. Our results merit further investigation.

Urachal mucinous adenocarcinoma: a case report.

Adenocarcinomas account for 0.5-2% of all bladder cancers. Urachal carcinoma is a rare neoplasm which represents 0.01% of all cancers in adults and account for one third of bladder adenocarcinomas. A 65-year-old white man with an urachal mucinous adenocarcinoma is reported. None of the known predisposing risk factors for bladder cancer -such as tobacco use and professional exposure to chemicals -were identified in his past medical history. The patient suffered from multiple sclerosis for almost 11 years and in the last 6 years he was treated with low doses of mitoxantrone. He underwent a partial cystectomy and en block excision of the umbilical ligament and remains disease-free after one year. The development of this rare neoplasm should not be clearly dissociated from multiple sclerosis, either aetiologically sharing an unidentified common causative factor or due to its treatment with mitoxantrone.

Gemcitabine and oral vinorelbine as salvage treatment in patients with advanced anthracycline- and taxane-pretreated breast cancer.

BACKGROUND: Despite progress achieved with new chemotherapeutic and endocrine agents, advanced breast cancer (ABC) remains a disease with poor prognosis. We sought to determine the efficacy of gemcitabine (GC) and oral vinorelbine (VB) in heavily preatreated ABC. PATIENTS AND METHODS: Patients previously treated with anthracyclines and taxanes in the metastatic setting with progressive disease were eligible. Treatment consisted of VB (60 mg/m2, orally) and GC (1000 mg/m2, intravenous infusion), every two weeks of a 28- day cycle. RESULTS: Thirty-one patients with ABC were enrolled. Toxicity was acceptable, mainly haematological. Three and 8 patients achieved a complete (9.6%) and partial (25.8%) response, respectively; ten patients (32.2%) had stable disease. Median time-to-progression was 5.3 months, while in responders 8.6 months. Median overall survival was 14 months. CONCLUSION: Oral VB and GC is an active and well-tolerated combination in anthracycline/taxane-pretreated ABC, representing an interesting option in this poor prognosis group of patients.

First-line chemotherapy with fluorouracil-epirubicin-navelbine (FEN) combination in advanced breast cancer.

BACKGROUND: A phase II study was carried out to determine the safety and efficacy of the combination of vinorelbine, epirubicin and 5-fluorouracil (FEN) as first-line chemotherapy in advanced breast cancer (BC). PATIENTS AND METHODS: Thirty-four women with advanced BC, aged 32-75 years (median 59), previously untreated for recurrence, were enrolled in the study. The treatment consisted of fluorouracil 600 mg/m2 on day 1, epirubicin 75 mg/m2 on day 1 and vinorelbine 25 mg/m2 on days 1 and 8, every 3 weeks, up to a maximum of 9 cycles. RESULTS: The efficacy appeared favourable with 18 objective responses (3 complete and 15 partial) and 9 disease stabilizations, giving an overall response rate of 53% (95% CI: 36-70). The median progression-free and overall survival was 6 and 18 months, respectively (95% CI: 4.8-7.8 and 16.2-22.2, respectively). Toxicity was acceptable; the main grade 3/4 toxicity was alopecia in 94% of patients, neutropenia in 44% and less frequently gastrointestinal toxicity (9%), anaemia (6%), mucositis (6%), thrombocytopenia (3%) and diarrhoea (3%). No treatment-related death occurred, CONCLUSION: Our results suggest that FEN, as first-line chemotherapy, is an active and well-tolerated treatment for patients with advanced breast cancer.

Multiple cutaneous acral metastases in a woman with breast adenocarcinoma treated with pegylated liposomal doxorubicin: incidental or aetiological association?

This paper reports the case of a 45-year-old female with histologically documented, multiple cutaneous metastases in the palmar and plantar surface of the fingers and toes originating from a breast adenocarcinoma after treatment with a docetaxel and pegylated liposomal doxorubicin regimen. The rarity of such a metastatic pattern from breast cancer and the eventual association with the chemotherapy administered are thoroughly discussed.