PHARMACOTHERAPY

Radium-223 in metastatic castration-resistant prostate cancer: a single centre experience

Radium-223 is one of the treatment options for patients with metastatic castration-resistant prostate cancer (mCRPC), based on the ALSYMPCA trail, a large randomised study.

In this retrospective study, the experience with radium-223 in patients with mCRPC, treated in a single centre, is reported in relation to the number of cycles of radium-223 given; reason of discontinuing radium-223 treatment, overall survival according to radium-223 treatments received; next treatment and interval to next treatment after discontinuing radium-223.

The Kaplan-Meier method was used to describe overall survival, and the log-rank was used to compare different groups.

Thirty-eight patients were analysed. A total of 26 patients (68.4%) completed all six cycles of radium-223, while twelve patients (31.6%) stopped treatment earlier. The reasons for discontinuing treatment early were progressive disease during treatment with radium-223 (four patients); myelotoxicity (one patient, who was previously treated for a small cell carcinoma of the ureter with six cycles of carboplatinum); intercurrent death due to non-prostate cancer-related diseases (four patients); patient refusal (one patient); complication due to co-morbid condition (one patient). And, one patient who stopped treatment after five cycles was lost to follow up.

Patients who completed all six cycles had a median survival time of 27.4 months (95% CI: 16.4-non applicable [NA; because the upper confidence limit never reaches the 50% survival]); and patients who completed one to four cycles 9.0 months (95% CI: 4.6-NA, log rank test: p<0.001).

Of the 26 patients who completed all six cycles, sixteen patients started another line of treatment for mCRPC after a median time of 30.0 weeks (95% CI: 18.1-NA) after the last injection of radium-223.

Radium-223 is an appropriate treatment for patients with mCRPC with a median overall survival of 27.4 months and a drug-free interval of 30 weeks after six cycles of radium-223.

(BELG J MED ONCOL 2019;13(1):16–20)

Current systemic treatment of hepatocellular carcinoma

Advanced hepatocellular carcinoma (HCC) has a poor prognosis and limited therapeutic options. Sorafenib (Nexavar®) was the first drug to demonstrate survival benefit. Recently Regorafenib (Stivarga®) proved to be effective as second-line treatment after progression on Sorafenib. Both are only approved in patients with good performance status and preserved liver function. Alternative treatment options with better efficacy and fewer side effects are still an important medical need. Very recently Lenvatinib (Lenvima®) was granted approval as alternative first-line therapy. Cabozantinib and Ramucirumab showed survival benefit compared to placebo, but are not yet available for clinical use. After promising phase I/II trials, phase III studies with other targeted systemic therapies are being performed. Immunotherapy is another challenging research field that is currently being assessed in clinical trials. Nivolumab (Opdivo®) has received accelerated FDA-approval as second-line therapy. Results are further awaited but will influence the care of patients with advanced hepatocellular carcinoma in the near future.

(BELG J MED ONCOL 2018;12(6):287–292)

Emerging M+ RCC treatments from EAU Guidelines

Thanks to our improved understanding of the molecular pathogenesis of metastatic renal cell carcinoma, multiple new treatment agents have appeared and extended our therapeutic possibilities. Novel molecular-targeted agents have vastly replaced cytokine therapies but pointed out new challenges in finding the optimal sequence and/or combination in treating metastatic renal cell carcinoma patients. This review focusses on the emerging therapeutic options according to the European Association of Urology guidelines in the rapidly changing renal cell carcinoma landscape.

(BELG J MED ONCOL 2018;12(6):293–300)

Treatment options in patients with early breast cancer and BRCA-mutations or family history of cancer

Women diagnosed with BRCA1/2 mutation positive breast cancer have an increased lifetime risk of contralateral breast cancer and ovarian cancer. They benefit from risk-reducing surgical strategies such as mastectomy and salpingo-oophorectomy. For patients with BRCA mutations and hormone-receptor positive breast cancer, the option of combined bilateral annexectomy and hormonal therapy with Aromatase Inhibitor can be discussed with high-risk patients. For triple negative breast cancer with BRCA mutation, there is some evidence that adding platinum-agents in the neoadjuvant setting improves the pathologic complete response. Lastly, ongoing clinical trials testing the efficacy of poly (ADP-ribose) polymerase inhibitor therapy in patients with BRCA1/2 mutations will be determinant for the future guideline recommendations in determining best treatment options for these patients.

(BELG J MED ONCOL 2018;12(5):239–246)

Locally advanced cancer of the uterine cervix: Diagnosis and multidisciplinary treatment

Patients treated for locally advanced cancer of the uterine cervix, FIGO stages IB2 to IVA, may expect a 5-year survival varying from 75% to 16%, respectively. Even though screening programs in Latin America and the Caribbean were established since the 1960´s, advanced stages continue to impact mortality in these countries. Morbidity and quality-of-life are compromised because most of the patients present with symptoms in these later stages. It is crucial to accurately determine tumour size and extension to surrounding organs, not only to establish prognosis, but also for therapy planning. Positron emission tomography combined with computed tomography is the preferred imaging modality but magnetic resonance imaging has high accuracy characterising the primary lesion. Concurrent cisplatin-based chemoradiotherapy is the standard nonsurgical approach, with a relative risk of death of 0.81 compared to the same radiation therapy alone, showing an absolute survival benefit at five years of 6%. Before or after chemoradiation, additional systemic therapy could be used to improve outcomes in patients with locally advanced cancer of the uterine cervix.

(BELG J MED ONCOL 2018:12(3):118–124)

How to overcome resistance to epidermal growth factor receptor tyrosine kinase inhibitors in patients with advanced epidermal growth factor receptor mutated non-small-cell lung cancer?

Summary

Targeted therapies have transformed the management of non–small-cell lung cancer and placed an increased emphasis on stratifying patients on the basis of the presence of oncogenic drivers. The best characterised molecular driver to date is epidermal growth factor receptor. Selective oral inhibitors of epidermal growth factor receptor that are superior to chemotherapy have become available in clinical practice. Unfortunately progression develops after a median of ten to twelve months. This article provides a framework for understanding clinically relevant resistance mechanisms to epidermal growth factor receptor-tyrosine kinase inhibitors and strategies to delay or overcome resistance, both those clinically available and those in development.

(BELG J MED ONCOL 2018;12(2):68–74)

Checkpoint inhibitors in the first-line treatment of non-small cell lung cancer

SUMMARY

Antibodies against programmed cell death-1 (PD-1) and its ligand (PD-L1) have become standard-of-care in the second-line treatment for advanced non-small cell lung cancer after failure of first-line chemotherapy. The observed durable responses as well as the favourable toxicity profile have moved these agents to first-line studies for advanced non-small cell lung cancer. In tumours with high PD-L1 expression, pembrolizumab is registered as the preferred first-line treatment. Further studies are currently focusing on combination strategies. The major future challenge will be selecting the optimal treatment strategy for the patient.

(BELG J MED ONCOL 2017;11(8):380–385)