J. Blokken PhD, PharmD

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.

Immunotherapy as frontline treatment for advanced hepatocellular cancer

For more than a decade, systemic treatment of advanced hepatocellular carcinoma (HCC) remained limited to the use of the tyrosine kinase inhibitor sorafenib, with lenvatinib being a non-inferior alternative to this standard of care. Recently, however, results of the phase III IMbrave 150 trial, demonstrated that the combination of atezolizumab and bevacizumab is associated with a significantly better progression-free and overall survival than sorafenib in the frontline treatment of patients with advanced HCC. This finding will have a dramatic impact on the treatment paradigm for these patients. In addition to atezolizumab-bevacizumab, several other immunotherapy-based treatment regimens are being evaluated in the treatment of advanced HCC.

Highlights in gynaecological cancers

In this overview, the key highlights from ESMO 2020 with respect to gynaecological cancers will be discussed. In advanced endometrial cancers, data were presented on the use of letrozole in combination with palbociclib. In addition, to this, promising clinical efficacy was seen for the antibody-drug conjugate tisotumab vedotin in the treatment of patient with recurrent or metastatic cervical cancer. Also in cervical cancer, a study was presented on the optimal management of cervical cancer patients with intraoperatively detected positive pelvic lymph nodes. In ovarian cancers, several updates were presented of pivotal trials evaluating PARP inhibitors. In addition, results if the phase III INOVATYON trial indicate that platinum-based regimens should remain the standard of care for patients with recurrent ovarian cancer who experienced disease progression within six-twelve months after their last line of platinum-based therapy. Finally, results were presented of the IMagyn050 trial assessing the efficacy and safety of bevacizumab in combination with atezolizumab in the treatment of patients newly diagnosed stage III-IV ovarian cancer.

Highlights in melanoma

At ESMO 2020, most attention in the melanoma field went to studies addressing the benefit of immunotherapy, alone or in combination with other drugs. First of all, updates on the use of immunotherapy in the adjuvant setting were provided for the Keynote-054 and the CheckMate 238 trials. In the advanced melanoma setting, several studies investigating combinations of immunotherapy with targeted agents will be addressed. In addition to this, the ILLUMINATE-204 trial investigates the potential of combining immunotherapy with intratumoral therapy. Similarly, a second study describes the value of local therapy in the treatment of solitary melanoma after progression upon checkpoint inhibitors. Finally, vaccination strategies with an IDO/ PD-L1 peptide vaccine and adjuvant dendritic cell vaccination will be discussed.

Highlights in respiratory oncology

At ESMO 2020, again many interesting studies in the field of respiratory oncology were presented. For non-metastatic non-small cell lung cancer (NSCLC), there was a focus on neoadjuvant immunotherapy, adjuvant treatment with osimertinib and post-operative conformal radiotherapy. When addressing metastatic NSCLC, much attention went to combination strategies such as combining EGFR and VEGF inhibitors, an EGFR-MET antibody plus a tyrosine kinase inhibitor or VEGF and PD-1 inhibitor combinations. In addition, the question was raised on whether immunotherapy can cure metastatic NSCLC. Finally, this overview will describe important results in the field of non-metastatic and metastatic small-cell lung cancer (SCLC).

Highlights in breast cancer

Summary

During the 2020 Virtual ASCO meeting, no less than 226 presentations were dedicated to breast cancer. It is beyond the scope of this article to discuss all these abstracts, but instead we try to focus on the data that are most relevant for your daily clinical practice.

(BELG J MED ONCOL 2020;14(5):191-200)