T. Feys MBA, MSc

Highlights in melanoma

The introduction of immune checkpoint inhibitors and the combined use of BRAF and MEK inhibitors dramatically changed the treatment landscape of advanced melanoma over the last decade. The success of these agents in the advanced setting formed the basis to also evaluate these drugs in less advanced disease stages. During ESMO 2018 updates were given on the adjuvant use of dabrafenib and trametinib in resected stage III melanoma patients. In addition to this, results were presented on the use of immune checkpoint inhibitors in the neo-adjuvant setting. In the advanced melanoma setting, the most important data came from the four-year survival update of the CheckMate 067 trial and the presentation of the Keynote-022 study, in which the immune checkpoint inhibitor pembrolizumab was used in combination with dabrafenib and trametinib in the first-line treatment of BRAF-mutation positive advanced melanoma.

Highlights in breast cancer

During ESMO 2018 an entire presidential session was dedicated to breast cancer. In addition to exciting immuno-oncology data in the treatment of triple negative breast cancer (TNBC), this session featured the presentation of the overall survival (OS) data of the phase III PALOMA-3 trial, evaluating the alpha-specific PI3K-inhibitor alpelisib in PI3KCA-mutant advanced breast cancer, and results of a clinical trial demonstrating improved outcomes when adding a histone deacetylase (HDAC) inhibitor to exemestane in hormone-receptor positive advanced breast cancer. In early breast cancer it was further demonstrated that non-compliance with adjuvant endocrine treatment is an under-appreciated and under-reported problem. In addition, the HOBOE-2 adds to the evidence that adjuvant bisphosphonates also improve the disease-free survival (DFS) in premenopausal luminal breast cancer patients who have received ovarian function suppression combined with an aromatase inhibitor. Finally, a subgroup analysis of the ShortHER trial suggests that for low- and intermediate risk cancer HER2-positive early breast cancer, 9 weeks of trastuzumab might be non-inferior to the standard 1-year treatment duration. However, the interpretation of this trial is challenging and as such, one year of trastuzumab should remain the standard for now.

Highlights in melanoma

The melanoma highlights from ASCO 2018 include data on the surgical management of sentinel lymph node (SLN) positive melanoma, updated results from the Checkmate 238 study evaluating adjuvant nivolumab or ipilimumab for resected stage III and IV melanoma, the overall survival (OS) data of the COLUMBUS trial assessing the combination of the BRAF inhibitor encorafenib with the MEK inhibitor binimetinib in the treatment of unresectable BRAF-mutant melanoma and two studies evaluating immunotherapy for unresectable Merkel cell carcinoma. For a more complete overview of melanoma data presented at ASCO 2018 please refer to the official congress website (www.am.asco.org).

Immunotherapy for locally advanced unresectable non-small cell lung cancer

The progress that has been made in the last decades in the treatment of stage IV non-small cell lung cancer (NSCLC) has overall not been translated in the curative setting of stage I to III disease. In fact, the list of failed clinical trials aimed at improving the cure rates in this setting is long. The recent successes with immune checkpoint inhibition in stage IV NSCLC formed the basis to also study these agents in the curative setting. The first clinical trials to yield results in this setting evaluate immune checkpoint inhibition as consolidation treatment following chemoradiotherapy in locally advanced, unresectable NSCLC. The PACIFIC trial demonstrated that consolidation therapy with PD-L1 inhibitor durvalumab significantly prolongs both the progression-free (PFS) and overall survival (OS) compared to placebo in patients with disease control after chemoradiotherapy for stage III unresectable NSCLC. These findings have recently led to the EMA indication of durvalumab as a treatment of locally advanced, unresectable NSCLC patients whose tumors express PD-L1 on ≥1% of tumor cells and whose disease has not progressed following platinum-based chemoradiation therapy. In addition to this, recent phase II data show that consolidation pembrolizumab following concurrent chemoradiotherapy substantially prolongs the time to metastasis or death in patients with inoperable stage III NSCLC. Finally, the phase II ETOP NICOLAS trial demonstrated that the addition of nivolumab to concurrent chemoradiotherapy is safe and tolerable in stage III NSCLC with promising efficacy signals. Together all these data support the further exploration of immune checkpoint inhibition in the curative NSCLC setting. Several trials are currently ongoing, including studies on the potential of adjuvant immune checkpoint inhibition in stage II and IIIA disease and trials in the pre-operative setting.

Highlights in thoracic oncology

ESMO 2017 featured the presentation of several practice changing studies in the field of lung cancer. With respect to immunotherapy, durvalumab showed a benefit for patients with Stage III non-small cell lung cancer (NSCLC) when taken after chemotherapy-radiation. This represents the first major study showing an immunotherapy benefit for patients with lung cancer that is not Stage IV.¹ A second key immunotherapy study showed that stage IV NSCLC patients who continued to take nivolumab beyond 1 year had a significantly longer progression-free survival (PFS) than patients who took the drug for 1 year.²

Also in the field of targeted therapy, ESMO 2017 may have induced a paradigm shift. In the phase III FLAURA study, the third-generation EGFR tyrosine kinase inhibitor (TKI) osimertinib, which is already approved for recurrent NSCLC patients harboring an EGFR^T790M mutation, was associated with a superior PFS to the current standard of care EGFR-targeted drugs. This was especially the case for patients with brain metastases.³ More positive data in NSCLC patients with brain involvement came from the ALUR trial and from a secondary analysis of the ALEX study, showing that alectinib can significantly decrease central nervous system (CNS) progression of NSCLC, both in the first-line and in the second-line setting.^4,5

In addition to this, the combination of the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib was shown to be an effective first treatment for BRAF^V600E mutated NSCLC.⁶

A final study worth mentioning in this introduction consists of the IFCT-0302 trial which demonstrated that frequent CT scans after surgery for early-stage lung cancer surgery did not improve survival. This should inform follow-up recommendations and should give patients some peace of mind that they don’t necessarily need CT scans every six months.⁷

(BELG J ONCOL 2017;11(7):317–325)

Highlights in melanoma

The melanoma abstracts discussed in this highlights report will focus on three main themes. First, three abstracts will be discussed addressing adjuvant therapy in patients with high-risk melanoma. Secondly, long-term data were presented of a phase III study assessing pembrolizumab in ipilimumab-naïve advanced melanoma patients, followed by the 5-year overall survival (OS) data of a study with dabrafenib and trametinib in BRAF^V600 mutant metastatic melanoma. The third and last part of this summary will discuss the data of three clinical studies looking into the treatment of melanoma patients with brain metastasis. For a more complete overview of melanoma data presented at ASCO 2017 we would like to refer to the official congress website (www.am.asco.org).

Highlights in breast cancer

This report will discuss a selection of key studies related to breast cancer discussed during the 2017 annual meeting of the American Society of Clinical Oncology. ASCO 2017 featured important new data generated with CDK4/6 inhibitors in patients with advanced breast cancer and included several abstracts considering the potential of PD-L1 inhibition for breast cancer. In addition to this, updates of several large phase III studies, including MARIANNE, ALLTO and APHINITY were presented. For a more complete overview of breast cancer news presented at ASCO 2017, we refer to the ASCO annual meeting website (https://meetings.asco.org/am/register-submit-abstracts).