Tom Feys MBA, MSc

Breast cancer highlights

(BELG J MED ONCOL 2016;10(8):308–13)

Broadening the possibilities for checkpoint inhibitors

The past years brought early reports suggesting that immune checkpoint inhibitors targeting PD-1 and PD-L1 are effective across a range of different cancer types, beyond melanoma and lung cancer. A particularly encouraging finding was that immunotherapy was effective against many tumors that were resistant to traditional treatments.

The CTLA-4 and PD-1/PD-L1 pathways: leading the way in cancer immunotherapy

The cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) and programmed death 1 (PD-1) / programmed death-ligand 1 (PD-L1) immune checkpoints are negative regulators of the T-cell immune function. Inhibition of these targets, resulting in an increased activation of the immune system, has led to new immunotherapies for melanoma, non–small cell lung cancer, and other cancers. To set the stage for the impressive clinical data that have been produced with these agents, this introductory article will describe the similarities and differences of both pathways and will touch upon the implications of their inhibition.

Melanoma and skin cancer highlights at ASCO 2016

Summary

To set the scene for the skin cancer updates presented at ASCO 2016, it is worth looking at the spectacular evolution in the survival of patients with advanced melanoma. In the nineties, the 1-year overall survival (OS) for patients with metastatic melanoma was low at only 25% to 35%. For decades, not a single treatment was able to improve the OS rates seen with dacarbazine-based chemotherapy. This trend of negative studies was broken in 2010 when ipilimumab was shown to increase the 1-year OS rate to 47%.¹ Shortly thereafter, the BRAF-inhibitor vemurafenib was shown to be associated with a 1-year OS rate of 56% in BRAF-mutated advanced melanoma patients.² Building further on these positive data with vemurafenib, dabrafenib was shown to increase this 1-year OS rate to 70%.³ In 2014, phase III data with the PD1 inhibitor nivolumab were presented. With nivolumab, 71% of patients were still alive after 1 year.⁴ This finding was confirmed in 2015 when a similar 71% 1-year OS rate was demonstrated with another PD1 inhibitor, pembrolizumab.⁵ 2015 also featured the presentation of 2 phase III studies evaluating combinations of a BRAF and a MEK inhibitor. In these studies, three quarters of patients was still alive after 1 year when they were treated with dabrafenib/trametinib, or vemurafenib/cobimetinib.^6,7 Finally, in 2016 phase II data of a study combining nivolumab and ipilimumab demonstrated a 1-year OS rate of 73%.8 Similarly, the 2-year OS rate has risen from 15% with dacarbazine-based therapy to 50% or more with PD1 inhibitors and the BRAF/MEK inhibitor combinations.^1-7 In the phase II study with nivolumab and ipilimumab, the 2-year OS rate was even higher at 64%.⁸ The three-year OS was shown to be 22% with ipilimumab, while long-term data of earlier phase studies with nivolumab and dabrafenib/trametinib show a 3-year OS of respectively 42% and 38%. Finally, the 5-year follow-up data with ipilimumab demonstrated the long-term benefit of this agent with 18% of patients still alive at that time point.⁹ Five-year follow-up data of the phase I study with nivolumab showed a 5-year OS rate of 32%.¹⁰

(BELG J MED ONCOL 2016;10(5):156–158)

Highlights in oncology 2015

Summary

This article is based on the 2016 clinical cancer advances article, published by the American Society of Clinical Oncology, and reviews the most important advances made in the different fields of oncology that are most likely to impact daily clinical practice.¹

(BELG J MED ONCOL 2016;10(2):49–57)

New oncology reimbursements in Belgium

Summary

Overview of Belgian reimbursement news.

(BELG J MED ONCOL 2016;10(2):81)

Gynaecological cancer task force