KEYNOTE-224: Durable responses, positive PFS, OS with pembrolizumab in advanced HCC
Pembrolizumab demonstrated promising results in several outcomes among patients with advanced hepatocellular carcinoma (HCC) whose disease progressed on or who were unable to tolerate treatment with sorafenib, findings from the KEYNOTE-224* trial show.
“Immunotherapy approaches, including immune checkpoint blockade, have shown initial promising results in advanced HCC,” said study investigator Professor Andrew X. Zhu from the Massachusetts General Hospital, Boston, Massachusetts, US, when presenting the findings at the ASCO 2018 Gastrointestinal Cancers Symposium (ASCO GI 2018).
“[In this study] pembrolizumab treatment demonstrated efficacy in patients with advanced HCC previously treated with sorafenib as evidenced by the durable responses and promising progression-free [PFS] and overall survival [OS],” said Zhu.
In this open label, phase II trial, 104 patients aged ≥18 years (median age 68 years, 82.7 percent male) with HCC exhibiting radiographic progression after or intolerant to treatment with sorafenib, ECOG status 0–1, BCLC** stage C or B, predicted life expectancy >3 months, and not amenable to curative treatment received intravenous pembrolizumab (200 mg Q3W) for up to 2 years or until disease progression, intolerable toxicity, investigator decision, or withdrawal of consent.
A majority of the patients were ECOG status 0 (60.6 percent), BCLC stage C (80.8 percent), and had progressed on sorafenib treatment (79.8 percent).
The objective response rate was 16.3 percent, with one patient achieving complete response, 16 achieving partial response, and 47 having stable disease. Median time to response was 2.1 months and 94 percent of patients were estimated to have a response duration of ≥6 months, with an 8.2-month median duration of response. [ASCO GI 2018, abstract 209]
At data cut-off, median PFS was 4.8 months and median OS was not reached, with 23 patients still undergoing treatment.
About 73 percent of patients experienced at least one treatment-related adverse event (TRAE) of any grade, while 25 percent experienced grade ≥3 TRAEs. TRAEs led to treatment discontinuation in seven patients and there was one death attributed to ulcerative oesophagitis (investigator-assessed). There were no incidences of hepatitis B or C flares, though three patients experienced immune-mediated hepatitis.
Of the TRAEs of any grade that affected ≥5 percent of patients, the most common were fatigue (21.2 percent), increased aspartate aminotransferase levels (12.5 percent), diarrhoea, and pruritus (9.6 percent each).
“Safety profile was generally comparable to what has been established for pembrolizumab monotherapy in other indications,” said Zhu.
At present, sorafenib is the standard-of-care systemic treatment for advanced HCC in the first-line setting, with regorafenib the only globally approved second-line treatment following sorafenib in certain patients with HCC, said Zhu, who highlighted that a randomized, phase III trial comparing pembrolizumab vs placebo in the second-line setting in this population is ongoing.