J. Blokken PhD, PharmD

Highlights in gastro-intestinal cancers

At ASCO 2021, the most important studies in gastro-intestinal (GI) cancer related to the use of immuno-therapy in cancers of the upper gastro-intestinal tract. For advanced oesophageal squamous cell carcinoma (ESCC), the CheckMate 648 trial demonstrated that both nivolumab plus chemotherapy and nivolumab plus ipilimumab represent a new potential first-line standard of care, especially for patients with a tumour PD-L1 expression of at least 1%. For adenocarcinoma of the oesophagus and oesophago-gastric junction, there is no evidence that peri-operative chemotherapy is unacceptably inferior to multimodal therapy. For tumours of the lower gastro-intestinal tract, the most important results came from the DESTINY-CRC01, CHRONOS, FIRE-4.5 and PANAMA studies.

(BELG J MED ONCOL 2021;15(5):248-53)

Highlights in radiotherapy

SABCS 2020 featured several interesting presentations in the field of radiotherapy. The PRIME 2 study investigated the impact of omitting postoperative whole breast radiotherapy in older, low-risk women with early invasive breast cancer. Outcomes of the phase III BIG 3-07/TROG 07.01 trial were also reported providing improved insights into the optimal radiation dose and fractionation schedule for non-low risk ductal carcinoma in situ of the breast. Other interesting topics included the comparison of patient and physician reports of toxicity after breast radiotherapy and the finding that radiation therapy improves survival in early-stage HER2-positive breast cancer with a high-levels of tumour infiltrating lymphocytes. Finally, we report on the results of a retrospective analysis assessing the feasibility of radiation therapy de-escalation in patients with stage I, node-negative, HER2-positive breast cancer.

Highlights in triple-negative breast cancer

Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer that is prone to early recurrence. In recent years, however, promising data were generated with immunotherapy-based treatment regimens in both the neoadjuvant and metastatic setting. Several updates of these studies were presented at SABCS 2020. In addition, the meeting featured several interesting abstracts discussing potential biomarkers that would facilitate a better treatment selection. In addition to immunotherapy, several novel therapeutics, including antibody-drug conjugates and targeted therapies are emerging in the treatment for patients with metastatic TNBC.

Highlights in HER2-positive breast cancer

In the field of Human Epidermal Growth Factor Receptor 2 (HER2) positive early breast cancer, an interesting Subpopulation Treatment Effect Pattern Plot (STEPP) analysis of the APHINITY trial was presented at SABCS 2020. In addition, BluePrint RNA sequencing was used in an attempt to predict the benefit of adjuvant pertuzumab in this trial. Other interesting data in early HER2-positive breast cancer came from the use of neratinib as extended adjuvant therapy. In the metastatic setting, results of the PERTAIN study, the first randomised phase II trial to assess the addition of pertuzumab to trastuzumab and an aromatase inhibitor in the presence or absence of induction chemotherapy, were presented. Finally, a long list of abstracts featured results with novel HER2-directed therapies, including the antibody-drug conjugate trastuzumab deruxtecan, the tyrosine kinase inhibitor tucatinib and the investigational monoclonal antibody margetuximab.

Immunotherapy for the treatment of triple-negative breast cancer

While immune checkpoint inhibitors (ICIs) demonstrated a convincing efficacy with durable responses in many cancer types, the single agent efficacy of ICIs in patients with advanced triple-negative breast cancer (TNBC) proved to be low. In a successful attempt to boost this clinical activity, ICIs were subsequently combined with chemotherapy in patients with metastatic TNBC. Following the positive results in the metastatic setting, ICIs are now also under evaluation in combination with neoadjuvant chemotherapy in patients with early TNBC. This review provides an overview of the results obtained with ICI in TNBC, from the disappointing results with ICI monotherapy, over the emerging data with ICI-chemotherapy combinations in the neoadjuvant setting to the pivotal, practice-changing results obtained with atezolizumab and atezolizumab in combination with chemotherapy in metastatic TNBC patients.

The emerging role of immunotherapy in small-cell lung cancer

In contrast to the impressive improvements that were made in the treatment of patients with non-small cell lung cancer, the treatment for patients with small-cell lung cancer (SCLC) remained largely unchanged during the past three decades. More recently, however, immune checkpoint inhibitors have been gaining momentum in this setting. In Belgium, patients with extensive stage (ES) SCLC now have the choice between two effective treatment regimens combining an immune checkpoint inhibitor with chemotherapy. In addition to this, several other immunotherapy-based therapies are being scrutinised in clinical trials with ES SCLC patients.

Synergism between CTLA-4 and PD-(L)1 inhibition: the nivolumab-ipilimumab story

In recent years, the approval of anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-programmed cell death protein 1 (PD-1) antibodies have led to significant improvements in disease outcomes for various cancers. Despite their long-term durable efficacy, the responses to immune checkpoint blockade are limited to a minority of patients. In an attempt to overcome this, the combination of CTLA-4 and PD-1 inhibitors is gaining momentum as a rational approach to improve outcomes.¹ This review describes the mechanism of action of both nivolumab and ipilimumab and discusses how the combined use of both drugs leads to potential synergism. The final part of the article assesses the extent to which this theoretical synergism is translated into a clinical benefit for cancer patients.