Initial Lenvatinib–Pembrolizumab Results ‘Promising’ For Advanced Gastric Cancer

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: Preliminary results from the EPOC1706 trial suggest that lenvatinib plus pembrolizumab might offer a novel combination therapy for patients with recurrent or metastatic adenocarcinoma of the stomach or gastro-oesophageal junction. 

After a median follow-up of 12.6 months, the primary endpoint of objective response was achieved by 69% of the 29 patients who were given a median 10 cycles of lenvatinib 20 mg/day plus pembrolizumab 200 mg every 3 weeks. 

One (3%) patient achieved a complete response and 66% had partial responses, while the remaining 31% of patients had stable disease, giving a disease control rate of 100%, report Kohei Shitara and co-investigators from the National Cancer Center Hospital East in Chiba, Japan. 

The objective response rates (ORRs) were comparable for patients given lenvatinib plus pembrolizumab as a first- or second-line regimen (71 vs 67%) and those with gastric versus gastro-oesophageal junction disease (68 vs 75%). 

Prespecified exploratory analysis indicated that the ORR may differ between the patients with a PD-L1 combined positive score (CPS) of at least 10, at least 1 and below 1, at 100%, 84% and 40%, respectively. And patients with a high tumour mutation burden (TMB, ≥ the median score of 10) had a higher ORR than those with a low TMB, at 82% versus 60%. 

At data cutoff, treatment was continuing in 28% of patients, while 72% had discontinued because of disease progression (n=19), surgery with curative intent after disease response (n=1) or patient refusal (n=1). Almost half (45%) of the objective responses were ongoing at this time. 

Median progression-free survival (PFS) was 7.1 months and median overall survival had not been reached, the team reports in The Lancet Oncology. 

PFS was a median 9.1 months for patients with a PD-L1 CPS of at least 1 versus 5.9 months for those with a CPS below 1, but the median durations of PFS in TMB-high and TMB-low patients were comparable at 9.8 and 9.5 months, respectively. 

The most common treatment-related adverse events with lenvatinib plus pembrolizumab were hypertension, proteinuria, palmar–plantar erythrodysaesthesia, hypothyroidism and reduced appetite. These included grade 3 events in 48% of patients, most commonly hypertension (38%), proteinuria (17%) and reduced platelet counts (7%); there were no grade 4 or 5 treatment-related adverse events. 

“[T]he combination of lenvatinib plus pembrolizumab had promising anti-tumour activity and a manageable safety profile in patients with advanced gastric cancer”, Kohei Shitara et al conclude. 

“On the basis of these results, a confirmatory randomised study will be planned soon”, they write.  

“A precise mode of action of this combination for advanced gastric cancer should also be elucidated by ongoing biomarker analysis in this study.” 

Reference  

Kawazoe A, Fukuoka S, Nakamura Y, et al. Lenvatinib plus pembrolizumab in patients with advanced gastric cancer in the first-line or second-line setting (EPOC1706): an open-label, single-arm phase 2 trial. Lancet Oncol; Advance online publication 23 June 2020. https://doi.org/10.1016/S1470-2045(20)30271-0