Response of advanced HCC to pembrolizumab and lenvatinib combination therapy despite monotherapy failure

Abstract

In recent years, immune checkpoint inhibitors (ICIs) were successfully introduced to cancer therapy, and these drugs have already become essential for the treatment of various noncurable tumors. However, monotherapy in advanced hepatocellular carcinoma (aHCC) failed to show statistically significant improvement.

Recently, the combination of atezolizumab and bevacizumab demonstrated efficacy of combining ICI and VEGF inhibition, further substantiating previous data on synergistic mechanisms among respective substance classes.

As TKI treatment is currently standard of care for aHCC, and ICIs are approved by the FDA and available in many areas of the world, numerous patients may have been treated with monotherapy of those drugs. However, it remains unclear if failure to monotherapy has an impact on combination therapy. We therefore report a patient well responding to combination therapy despite previous failures to TKI and ICI monotherapy.

Zusammenfassung

In den letzten Jahren wurden Immuncheckpointinhibitoren (ICIs) erfolgreich in die Krebstherapie eingeführt. Für einige Tumorentitäten sind diese Substanzen bereits unverzichtbarer Bestandteil der therapeutischen Optionen geworden. Beim fortgeschrittenen hepatozellulären Karzinom (aHCC) zeigte sich hingegen für die Monotherapie bisher keine statistisch signifikante Verbesserung des Patientenüberlebens.

Kürzlich wurde jedoch für die Kombination von Atezolizumab und Bevacizumab eine sehr gute Wirksamkeit gezeigt. Die Wirksamkeit einer Kombination von ICI- und VEGF-Hemmung, aber auch frühe Daten zu synergistischen Mechanismen der Substanzklassen wurden so weiter untermauert.

Da die TKI-Behandlung derzeit der Standard der aHCC-Behandlung ist und ICIs von der FDA zugelassen und in vielen anderen Regionen der Welt erhältlich sind, wurden trotz fehlender Zulassung in Europa zahlreiche Patienten mit einer Monotherapie dieser Medikamente behandelt. Es ist jedoch unklar, ob ein Nichtansprechen auf diese Substanzen in der Monotherapie Bedeutung für die Kombination hat. Wir berichten über eine erste Patientin, die trotz vorausgegangenen Nichtansprechens auf TKI- und ICI-Monotherapie sehr gut auf die Kombinationstherapie angesprochen hat.

Key words

PD-1 - tyrosine kinase inhibitor - lenvatinib - pembrolizumab - atezolizumab - bevacizumab - nivolumab - immunotherapy - liver cancer - HCC

Schlüsselwörter

PD-1 - tyrosine kinase inhibitor - TKI - Lenvatinib - Pembrolizumab - Aatezolizumab - Bevacizumab - Nivolumab - Immuntherapie - Leberzellkarzinom - HCC

Publikationsverlauf

Eingereicht: 27. Januar 2020

Angenommen: 23. Mai 2020

Artikel online veröffentlicht:
12. August 2020

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