Optimizing the management of HER2-negative metastatic breast cancer in the era of PARP inhibitors-proceedings from breast cancer expert group meeting.

The therapeutic landscape of human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC) has evolved considerably with the introduction of newer targeted agents such as poly-ADP ribose polymerase inhibitors (PARPi), novel chemotherapeutic agents, immunotherapy, and endocrine therapies. In this scenario, optimizing the appropriate treatment sequence is a daunting task for clinicians. To develop evidence-based answers to key clinical questions on treatment selection and appropriate treatment sequence for the management of patients with HER2- mBC in the era of PARPi, a breast cancer expert group meeting was convened. The expert panel comprised of eight key opinion leaders from Argentina, Brazil, Colombia, Egypt, Mexico, Moscow, South Korea, and the United Arab Emirates, who convened and reviewed the literature, discussed the clinical practices across the participating regions, and formulated answers to key clinical questions for optimizing the management of HER2- mBC. In this review, evidence-based answers have been provided pertaining to (I) the specific mBC population to be considered for BRCA testing, optimal time point of BRCA testing, and genetic counselling in mBC patients; (II) the role of PARPi versus platinum therapy in HER2- mBC patients in the metastatic setting; (III) sequencing treatment in metastatic triple-negative breast cancer (TNBC) and hormone receptor-positive HER2- mBC patients, and defining the place of PARPi in the sequencing algorithms; and (IV) the need for a breast cancer registry for patients with HER2- mBC. This expert review will serve as a comprehensive guide to clinicians for optimizing BRCA testing and managing patients with BRCA mutation (BRCAm) and HER2- mBC. The data collected from the proposed HER2- mBC registry will help understand the treatment practices, identify unmet needs, and develop strategic policies regionally to help improve access to optimized care of HER2- mBC.

A descriptive study of plasma cell dyscrasias in Egyptian population.

BACKGROUND: Plasma cell dyscrasias (PCDs) refer to a spectrum of disorders characterized by the monoclonal proliferation of lymphoplasmacytic cells in the bone marrow and, sometimes, tissue deposition of monoclonal immunoglobulins or their components. These disorders include multiple myeloma (MM) and Waldenström's macroglobulinemia, as well as rare conditions such as light-chain deposition disease (LCDD) and heavy-chain diseases (HCDs). The worldwide annual incidence of MM is estimated at 86,000, which is approximately 0.8% of all new cancer cases. PURPOSE: Our retrospective study aims to highlight the immunologic and epidemiological features of PCDs mainly MM in Egyptian patients and compare our results with those of other populations. METHODS: Two hundred seventeen Egyptian patients with PCD were enrolled in the study. Serum, urine protein electrophoresis and immunofixation were used to demonstrate M protein. RESULTS: One hundred thirty-eight patients (63.6%) had IgG monoclonal band, 38 patients (17.5%) had IgA, 12 patients (5.5%) had Waldenström's macroglobulinemia (IgM monoclonal band) and 29 patients (13.4%) were light chain myeloma. One hundred fifty-one (70%) were Kappa chain positive and 66 patients (30%) were lumbda positive. Conventional cytogenetics was available for 40 patients; of them12 patients (30%) showed 13q-. Mean OS was 37.5months (1-84months). Survival analysis was statistically insignificant according to age, sex and ISS or type of treatment (P value>0.05). CONCLUSION: Long term follow up is required to further define the role of different therapeutic lines of treatment including ASCT in the various stages of PCD based on OS data.

Prospective study evaluating the radiosensitizing effect of reduced doses of temozolomide in the treatment of Egyptian patients with glioblastoma multiforme.

PURPOSE: In view of the documented toxicity of continuous daily radiosensitizer doses of temozolomide concomitant with radiation in the treatment of glioblastoma multiforme, we aimed to compare it with a different schedule of abbreviated radiosensitizer dosing. PATIENTS AND METHODS: This was a randomized prospective study comparing toxicity and survival in 60 Egyptian patients with glioblastoma multiforme. Patients in arm I received temozolomide at a dose of 75 mg/m(2) daily with radiotherapy for 42 days, starting 4 weeks after surgery and reaching to a total radiation dose of 60 Gy/30 Fractions/6 weeks, while patients in arm II received temozolomide at a dose of 75 mg/m(2) concomitantly with the same radiotherapy schedule daily in the first and last weeks of the same radiotherapy program. RESULTS: Common grade 1-2 adverse events were malaise in 28 patients (46.7%), followed by alopecia (40%) and nausea (26.7%). Grade 3-4 convulsion and decreased level of consciousness was seen in only four patients who were all from arm I. The median progression-free survival (PFS) for the entire study population was 10.6 months (95% confidence interval [CI] 7.3-14), and PFS at 12 months was 32%. The median PFS in arm I was 8.8 months (95% CI 5.9-11.7) and in arm II 11.5 months (95% CI 8.9-14.2), and PFS at 12 months for both arms was 32% and 30% respectively (P=0.571). The median overall survival (OS) of the whole group of patients was 14.2 months (95% CI 13-15.5), and OS was 70% at 12 months and 25% at 18 months. The median OS for patients in arm I was 12.3 months (95% CI 7.7-16.9), whereas in arm II it was 14.3 months (95% CI 14-14.7) (P=0.83). CONCLUSION: Reduced radiosensitizer dosing of temozolomide concomitant with radiotherapy in glioblastoma multiforme exhibited comparable efficacy with a classic continuous daily schedule, though with better tolerability.

Adjuvant chemotherapy for luminal A breast cancer: a prospective study comparing two popular chemotherapy regimens.

INTRODUCTION: Based on the variable benefit of taxanes in the adjuvant setting of early breast cancer in certain tumor phenotypes, especially in human epidermal growth factor receptor (HER)2-positive and triple-negative disease, and with the observation of a lesser benefit in luminal A, this research article aimed at exploring the value of docetaxel in patients with an estrogen receptor-positive, HER2-negative disease phenotype, who might not derive the same benefits as those with other phenotypes. PATIENTS AND METHODS: This was a randomized prospective study comparing disease-free survival (DFS) and safety profile of sequential adjuvant three cycles Fluorouracil, Epirubicin, Cyclophosphamide followed by three cycles Docetaxel (FEC-D) versus six cycles classic Fluorouracil, Epirubicin, Cyclophosphamide (FEC)-100 in 60 Egyptian women who presented to Dar Al Fouad Hospital during the period June 2007 to July 2008 with (pT1-2 pN0-3 M0). The primary end point was DFS in a follow-up period of 4 years. The secondary end point was toxicity profile. RESULTS: Four-year DFS rates were comparable in both arms: 73.3% ± 8.1% in the FEC-D arm versus 76.5% ± 7.8% in the FEC-100 arm (P = 0.83). N3 and grade III subgroups achieved the worst DFS in both subgroups (P = 0.001 and P = 0.214, respectively). The rate of nausea and vomiting was higher in the FEC-100 arm (P = 0.49), while grade III-IV neutropenia and febrile neutropenia incidence was similar between both arms. CONCLUSION: Sequential adjuvant chemotherapy with FEC followed by docetaxel achieved comparable DFS results to FEC alone in luminal A phenotype subgroups of breast cancer.

Comparative study analyzing survival and safety of bevacizumab/carboplatin/paclitaxel and cisplatin/pemetrexed in chemotherapy-naïve patients with advanced non-squamous bronchogenic carcinoma not harboring EGFR mutation.

PURPOSE: The majority of Egyptian patients with lung cancer present at a late stage of the disease. Bevacizumab/carboplatin/paclitaxel, as well as cisplatin plus pemetrexed, are both standard regimens for advanced non-squamous bronchogenic cancer. This study compares both regimens, in terms of efficacy and toxicity profile, in Egyptian patients. PATIENTS AND METHODS: This is a randomized Phase II study comparing toxicity profile and survival in 41 chemotherapy-naïve patients with stage IIIB or IV non-squamous NSCLC, with an ECOG performance status of 0 to 2. The epidermal growth factor receptor (EGFR) mutation detection was performed prior to treatment of all patients. Patients in the first group received: bevacizumab 7.5 mg/m(2) on Day 1 and Day 15; carboplatin area under the curve-5 on Day 1; and paclitaxel 60 mg/m(2) on Day 1, Day 8, and Day 15 every 4 weeks. In the second group, patients received cisplatin 75 mg/m(2) and pemetrexed 500 mg/m(2) every 3 weeks. RESULTS: The combination of bevacizumab/carboplatin/paclitaxel demonstrated higher Grade III-IV toxicity than cisplatin/pemetrexed regarding sensory/motor neuropathy (P = 0.06), DVT (P = 0.23), proteinuria (P = 0.23), and hypertension (P = 0.11), as well as Grade II alopecia (P = 0.001); however, no significant difference in toxicities between both arms was recorded regarding nausea and vomiting (P = 0.66), hematological toxicity, febrile neutropenia (P = 1) and fatigue (P = 0.66). Progression-free survival was similar for both treatment arms with a median of 6 months (P = 0.978). Overall median survival was comparable in both arms, 16.07 months versus 16.01 months (P = 0.89). CONCLUSION: Bevacizumab/carboplatin/paclitaxel and cisplatin/pemetrexed provided meaningful and comparable efficacy in advanced non-squamous bronchogenic carcinoma not harboring EGFR mutation. No significant difference in toxicity was observed between both treatment arms, apart from bevacizumab/carboplatin/paclitaxel-related risks as DVT, hypertension, proteinuria, sensory/motor neuropathy, and alopecia.

Comparative study analyzing survival and safety of bevacizumab/carboplatin/paclitaxel versus carboplatin/docetaxel in initial treatment of metastatic Her-2-negative breast cancer.

PURPOSE: In view of the previous reports demonstrating the positive outcome of bevacizumab in metastatic breast cancer, we aimed at comparing the role of bevacizumab-based metronomic combination with taxane (paclitaxel) versus a different taxane (docetaxel)-based regimen in addition to carboplatin as initial treatment for metastatic Her-2-negative breast cancer. PATIENTS AND METHODS: This is a randomized Phase III study comparing the progression-free survival (PFS) and safety in Her-2-negative female patients with initial diagnosis of metastatic breast cancer with World Health Organization performance status of 0-II. Forty-one patients were randomized from September 2008 to July 2009 to receive either; (1) bevacizumab 5 mg/kg day 1 and day 15, carboplatin area under the curve (AUC)-2 day 1, day 8, and day 15, and paclitaxel 60 mg/m(2) day 1, day 8, and day 15 (arm-I); or (2) carboplatin AUC-5 day 1, docetaxel 75 mg/m(2) day 1 (arm-II). The Kaplan-Meier method was used for estimating survival; log-rank test for comparing survival curves. The primary end point was PFS, and secondary end points were overall survival (OS) and safety. RESULTS: PFS was 10 months in arm I versus 10.2 months in arm II (P = 0.9). The OS rate was similar in both arms: 37.6 months for arm I versus 37.4 months for arm II (P = 0.92). The toxicity revealed higher incidence of hypertension and proteinuria in arm I; however, with higher incidence of grade III-IV neutropenia and neutropenic fever in arm II. No treatment-related mortality was recorded. CONCLUSION: Bevacizumab/carboplatin/paclitaxel and carboplatin/docetaxel show comparable PFS and OS with different toxicity profiles.

Palliative fractionated radiotherapy for bone metastases clinical and biological assessment of single versus multiple fractions.

BACKGROUND: Radiotherapy is effective in controlling pain from bone metastases which is a direct result of bone resorption. The urine resorption marker DPD proved important in assessing effectiveness of palliative radiotherapy to bone metastases. There is still controversy about the optimum adopted fractionation regimen. The aim of this study is to compare single fraction 8Gy with the standard treatment course of 30Gy/10 fractions/ 2weeks and to a third regimen of 20Gy/5 fractions/ 1week regarding factors impacting on QoL in terms of improved pain, mobility, analgesia scores, PS. The decrease of urine DPD was included as an objective parameter of response. PATIENTS AND METHODS: A prospective phase lll controlled study of palliative radiotherapy was conducted on 60 patients with bone metastases from known primary sites divided into 3 groups each of 20 patients balanced in age, sex, and type of malignancy, to be treated with one of three RT regimens. Assessment was done before and 6 weeks after treatment completion according to an established scoring system. RESULTS: Pain and analgesia scores were improved in the group receiving 30Gy/10 fr. regimen (p = 0.002 = 0.003) with no significant improvement of mobility (p=0.16) or PS (p=0.08). Urine DPD was decreased in this group by 43% in 9/20 patients. The group receiving single fraction of 8 Gy showed a significant improvement of scores of pain (p=0.008), analgesia (p=0.01), mobility (p=0.001), PS (p=0.01) and decrease in urine DPD by 33% in 7/20 patients. The group receiving 20Gy/5 fr. protocol achieved improved scores of pain (p=0.002), analgesia (p=0.008), mobility (p=0.03), and a decrease of ,-DPD by 56% in13/20 patients which was significantly better than the group receiving single 8Gy fraction,(p=0.03). There was a trend towards an increased number of reirradiations in patients receiving single fraction 8Gy, though not significant, whereas reirradiation was significantly correlated with the high initial ,-DPD level within all groups. CONCLUSION: The 20Gy/5fr. regimen seems to be superior to both the standard 30Gy/10fr. and the single fraction 8Gy as it achieved significant improvement of three clinical criteria, pain, analgesia and mobility concomitantly with significant decrease in urine DPD. Urine resorption markers confer subjective evaluation of radiotherapy response in patients with bone metastases. The high initial ,-DPD level was significantly correlated with the need to reirradiation. Key Words: Fractionated radiotherapy , Bone metastases , Bone resorption markers.