MAGE-A10 Protein Expression in Advanced High Grade Serous Ovarian Cancer Is Associated with Resistance to First-Line Platinum-Based Chemotherapy.

Ovarian cancer has a dismal prognosis. Standard treatment following surgery relies on platinum-based chemotherapy. However, sizeable percentages of patients are unresponsive. Identification of markers predicting the response to chemotherapy might help select eligible patients and spare non-responding patients from treatment-associated toxicity. Cancer/testis antigens (CTAs) are expressed by healthy germ cells and malignant cells of diverse histological origin. This expression profile identifies them as attractive targets for cancer immunotherapies. We analyzed the correlations between expression of MAGE-A10 and New York esophageal-1 cancer (NY-ESO-1) CTAs at the protein level and the effectiveness of platinum-based chemotherapy in patients with advanced-stage high-grade serous ovarian carcinoma (HGSOC). MAGE-A10 and NY-ESO-1 protein expression was analyzed by immunohistochemistry (IHC) in formalin-fixed, paraffin-embedded samples from 93 patients with advanced-stage HGSOC treated at our institutions between January 1996 and December 2013. The correlation between the expression of these markers and response to platinum-based chemotherapy, evaluated according to RECIST 1.1 criteria and platinum sensitivity, measured as platinum-free interval (PFI), progression free (PFS), and overall survival (OS) was explored. The MAGE-A10 protein expression predicted unresponsiveness to platinum-based chemotherapy (p = 0.005), poor platinum sensitivity (p < 0.001), poor PFS (p < 0.001), and OS (p < 0.001). Multivariate analysis identified MAGE-A10 protein expression as an independent predictor of poor platinum sensitivity (p = 0.005) and shorter OS (p < 0.001). Instead, no correlation was observed between the NY-ESO-1 protein expression and response to platinum-based chemotherapy (p = 0.832), platinum sensitivity (p = 0.168), PFS (p = 0.126), and OS (p = 0.335). The MAGE-A10 protein expression reliably identified advanced-stage HGSOC unresponsive to platinum-based chemotherapy. Targeted immunotherapy could represent an important alternative therapeutic option in these cancers.

Real-World Efficacy and Safety of Bevacizumab in the First-Line Treatment of Metastatic Cervical Cancer: A Cohort Study in the Total Population of Croatian Patients.

BACKGROUND: Although today it is almost preventable, cervical cancer still represents a significant cancer burden, especially in some developing parts of the world. Since the introduction of bevacizumab in the first-line treatment of metastatic disease, improvements of the outcomes were noted. However, results from randomized controlled trials are often hard to recreate in the real-world setting. OBJECTIVE: To assess the real-world efficacy and safety of bevacizumab as a first-line treatment of advanced cervical cancer. METHODS: We conducted a retrospective cohort study on the total population of Croatian patients diagnosed with metastatic cervical cancer from 2016 to 2019 who were treated with bevacizumab in combination with cisplatin and paclitaxel (TCB) in the first line. The comparison group was the consecutive sample of patients treated with chemotherapy alone. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), objective response rate, incidence of adverse events, and the proportion of treatment discontinuation. RESULTS: We enrolled 67 patients treated with TCB and a control group of 62 patients treated with chemotherapy alone. The TCB cohort had significantly longer unadjusted OS with a median of 27.0 (95% CI 18.5; not calculable) months, compared to 15.5 (10.7; 30.1) months in the chemotherapy-alone cohort. Adjusted OS was not significantly different. PFS was significantly longer for the TCB cohort, with a median of 10.6 (95% CI 8.5; 15.4) months, than for the chemotherapy-alone cohort, with a median of 5.4 (95% CI 3.9; 9.1) months, even after adjustment for baseline covariates (HRadjusted = 0.60; 95% CI 0.39; 0.94; p=0.027; false discovery rate <5%). CONCLUSIONS: In a real-world setting, TCB as a first-line treatment of metastatic cervical cancer was associated with longer PFS, better objective disease control rate, and acceptable toxicity profile in comparison to chemotherapy alone. These results may indicate its utility and potential applicability in other parts of the developing world.

Early HER2-Positive Breast Cancer: Current Treatment and Novel Approaches.

BACKGROUND: Trastuzumab significantly improves outcomes in early HER2-positive breast cancer, irrespectively of any prognostic or predictive factors. Unfortunately, about a quarter of patients receiving neoadjuvant trastuzumab experience disease recurrence, revealing the unquestionable need for further improvement of treatment outcomes. SUMMARY: Adding HER2 blockade to adjuvant trastuzumab with pertuzumab and neratinib improves invasive disease-free survival (IDFS), particularly for those at highest risk of recurrence. A shift toward a neoadjuvant strategy for patients with a higher risk of recurrence could result in further treatment optimization. For patients without a pathological complete response (pCR) after the neoadjuvant part of the therapy, a switch to adjuvant trastuzumab emtansine significantly improves IDFS and distant recurrence-free survival and shows a trend towards improved overall survival (OS). On the other hand, for low-risk patients, chemotherapy deescalation should be strongly considered with the use of trastuzumab monotherapy as an anti-HER2 backbone. KEY MESSAGES: Neoadjuvant therapy should be offered for a significant proportion of HER2-positive early breast cancer patients with a higher risk of recurrence. Postneoadjuvant treatment should be tailored according to the initial stage of disease and the response to neoadjuvant treatment.

Long follow-up of patients with locally advanced cervical cancer treated with concomitant chemobrachyradiotherapy with cisplatin and ifosfamide followed by consolidation chemotherapy.

OBJECTIVES: Locally advanced cervical cancer (LACC) is one of the leading health problems of the developing countries. We present long-term outcomes of treatment with a concomitant chemobrachyradiotherapy followed by consolidation chemotherapy regimen. MATERIALS AND METHODS: We treated 118 patients with LACC (International Federation of Gynecology and Obstetrics stages IB2-IVA) with external radiotherapy (50 Gy in 25 fractions) and concomitant chemobrachyradiotherapy (low-dose rate). Chemotherapy was applied during brachyradiotherapy (cisplatin on day 1 in combination with 24-hour infusion of ifosfamide and mesna uroprotection). Four cycles of consolidation chemotherapy were given starting 4 weeks after the second concomitant chemobrachyradiotherapy cycle. RESULTS: After median follow-up period of 99.3 months, we observed acceptable acute and late toxicity, local control rate of 97.5%, and an overall survival of 74.6% at 96 months. CONCLUSIONS: Chemobrachyradiotherapy regimen followed by consolidation chemotherapy described in this article is a valuable treatment option for LACC.