J. Blokken PhD, PharmD

Biomarkers for immune checkpoint inhibition

Summary

Immune checkpoint inhibitors are effective in restoring the T-cell mediated immune response and can achieve a deep and durable response in a small subset of cancer patients. As only 15% to 25% of the patients with advanced NSCLC will benefit from immunotherapy, a predictive biomarker is required to select patients who will potentially respond. To date, the most intensively studied potential biomarkers consist of the programmed death ligand 1 (PD-L1) expression, the tumour mutational burden (TMB) and the tumour micro-environment (TME), each with its own advantages and challenges. This article will briefly describe each of these biomarkers and will touch upon the relationship between certain genetic modifiers and a response to immunotherapy.

Journal Scan

SUMMARY

The goal of this new section in the BJMO is to provide a snapshot of pivotal studies published in recent issues of the most important international journals focusing on oncology. Importantly, the selection of the studies discussed here is the sole responsibility of the publisher and was not influenced by third parties. Do you miss an important study, or did you read a hidden jewel that deserves to be shared with your colleagues? Please let us know (editor@bjmo.be) and we will make sure to include it in the journal scan section of the next BJMO issue.

(BELG J MED ONCOL 2020;14(2):80–3)

Immuno-oncology combinations: rationale and clinical implications in melanoma, renal cell carcinoma and lung cancer

ABSTRACT

Over the past years, immune checkpoint inhibitors have been widely used for the treatment of a broad range of malignancies. Unfortunately, only a proportion of patients derives long-term benefit from these therapeutics. In fact, a majority of patients fails to respond to immune checkpoint inhibition, while others relapse after a certain time. In an attempt to increase the response rate of tumours to these drugs, investigators have looked into the potential of combining different immunotherapeutic agents. Since inhibitors of the immune checkpoints CTLA-4 and PD-(L)1 have different modes of action and given the fact that blocking one of both pathways results in an upregulation of the other, provide a theoretical rationale to combine these agents. This review provides an overview of clinical studies evaluating combinations of CTLA-4 and PD-(L)1 inhibitors in the treatment of melanoma, renal cell carcinoma and non-small-cell lung cancer.

The 13^th Belgian symposium on the integration of molecular biology advances into oncology clinical practice (BSMO/Bordet meeting)

SUMMARY

On the 22^nd and 23^rd of November 2019, the Jules Bordet Institute and the Belgian Society of Medical Oncology (BSMO) hosted the 13^th Belgian symposium on the integration of molecular biology advances into oncology clinical practice. In the course of the symposium, a fine selection of Belgian and international key opinion leaders discussed the clinical impact of molecular biology advances in a plethora of cancer types.

(BELG J MED ONCOL 2020;14(1):31–41)

Highlights in melanoma

The introduction of immune checkpoint inhibitors highly impacted the treatment landscape of melanoma over the last decade. At ESMO 2019, several abstracts again proved the clinical potential of these agents in the treatment of melanoma, both in (neo)adjuvant as in the advanced setting. In addition to this, promising results were presented with talimogene laherparepvec in early and in metastatic melanoma. Finally, several abstracts also discussed combinations of targeted agents and immunotherapy in patients with advanced melanoma.

Highlights in breast cancer

ABSTRACT

The 2019 edition of the annual ESMO meeting proved to be a grand cru when it comes to breast cancer studies. In early triple negative breast cancer (TNBC), the KEYNOTE-522 trial demonstrated a significant improvement of pathological complete response rate with the addition of pembrolizumab to neoadjuvant chemotherapy, irrespective of PD-L1 status. In addition to this, the prognostic value of tumour-infiltrating lymphocytes was confirmed in a pooled analysis of patients with TNBC who did not received adjuvant chemotherapy. In the field of metastatic breast cancer, much attention went to overall survival data that were presented for the CDK4/6-inhibitors ribociclib and abemaciclib in combination with fulvestrant (MONALEESA-3, MONARCH 2). Interesting results of the phase III BROCADE3 trial were presented in which the addition of the PARP inhibitor veliparib to carboplatin and paclitaxel was evaluated in patients with advanced HER2-negative breast cancer and a germline BRCA mutation. Regarding checkpoint inhibitors in metastatic TNBC, a read-out of a phase III trial with pembrolizumab compared to standard chemotherapy in second- and third-line was presented, as well as important translational data on different immunohistochemical PD-L1 assays from IMpassion130. Finally, two oral presentations focused on the use of CDK4/6-inhibitors in different combination regimens in metastatic HER2-positive breast cancer (MonarcHER) and in TNBC.