The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has adopted positive
opinions recommending approval of the combination of lenvatinib, the oral multiple receptor tyrosine kinase inhibitor, plus pembrolizumab, an anti-PD-1 therapy, for two different indications in advanced EC and advanced RCC.

The positive opinion for advanced or recurrent EC is for the treatment of adult patients who have disease progression on, or following, prior treatment with a platinum-containing therapy in any setting and are not candidates for curative surgery or radiation.

People with advanced or recurrent EC typically have a poor prognosis, largely due to a lack of diverse treatment options in the metastatic setting.

“The CHMP’s recommendation is welcome news for clinicians, particularly for those of us caring for patients with advanced endometrial cancer where there has been very little treatment innovation in the last four decades,” said Professor Nicoletta Colombo, Associate Professor of Obstetrics and Gynaecology at the University of Milan-Bicocca and European Institute of Oncology.

“Up until now there had been no standard, recommended treatment for those patients who are unable to undergo surgery and have progressed on chemotherapy-based regimes. If approved, this will significantly expand our ability to support these patients and improve the prognosis of these patients with high unmet needs.”

For RCC, the positive opinion is for the first-line treatment of adult patients with advanced disease. The European Commission’s decision on both CHMP recommendations for marketing authorisation in the European Union is expected by the end of 2021.

“Up to a third of patients with renal cell carcinoma will be diagnosed with late-stage disease – when prognosis is often worse – highlighting the need for new treatment options for these patients in Europe,” said Professor Viktor Gruenwald, Interdisciplinary Genitourinary Oncology, University Hospital Essen, Germany.

“The introduction of this particular combination in the first-line setting will further expand the ever-growing armoury of tools that clinicians have to manage metastatic disease and extend the overall survival of patients.”

“The treatment of advanced renal cell carcinoma and endometrial cancer remains highly challenging for clinicians, and this is magnified by the lack of treatment options currently available to patients,” said Miguel Marcão, Vice President, Eisai EMEA Oncology Business Group.

“We are pleased that the CHMP has recognised the important role of the lenvatinib plus pembrolizumab combination in treating these advanced cancers as we take a critical step forward in our journey of delivering new options to patients in Europe and across the world,” added Dr. Gregory Lubiniecki, Vice President, Clinical Research, Merck Research Laboratories.

The positive CHMP opinion for EC is based on data from the pivotal Phase 3 trial: KEYNOTE-775 / Study 309 which evaluated the combination in patients with advanced EC.

In the trial, lenvatinib plus pembrolizumab demonstrated statistically significant improvements in the study’s co-primary
endpoints of OS, reducing the risk of death by 32% (HR=0.68 [95% CI, 0.56-0.84]; p=0.0001), and PFS, reducing the risk of disease progression or death by 40% (HR=0.60 [95% CI, 0.50-0.72]; p<0.0001), versus chemotherapy (investigator’s choice of doxorubicin or paclitaxel).

The most common adverse reactions of these patients (all grades ≥20%) for lenvatinib plus pembrolizumab were hypertension (64%), hypothyroidism (57%), diarrhoea (54%), nausea (50%), decreased appetite (45%), vomiting (37%), decreased weight (34%), fatigue (33%), arthralgia (31%), proteinuria (29%), anaemia (26%), constipation (26%), urinary tract infection (26%), headache (25%) and asthenia (24%).

The positive CHMP opinion for the combination in adults with advanced RCC is based on the pivotal Phase 3 trial CLEAR (Study 307) / KEYNOTE-581. In the trial, lenvatinib plus pembrolizumab demonstrated statistically significant improvements versus sunitinib in the efficacy outcome measures of progression-free survival (PFS), reducing the risk of disease progression or death by 61% (HR=0.39 [95% CI, 0.32-0.49]; p<0.001) with a median PFS of 23.9 months versus 9.2 months for sunitinib and overall survival (OS), reducing the risk of death by 34% (HR=0.66 [95% CI, 0.49-0.88]; p=0.005) versus sunitinib.

The most common adverse reactions (all grades ≥25%) for lenvatinib plus pembrolizumab were diarrhoea (61%), hypertension (55%), hypothyroidism (47%), decreased appetite (40%), fatigue (40%), nausea (36%), stomatitis (35%), dysphonia (30%), weight loss (30%), proteinuria (30%), PPE syndrome (29%), arthralgia (28%), rash (27%), vomiting (26%) and constipation (25%).

Source: Eisai