First anti-cancer combination for advanced endometrial cancer receives final approval

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March 9, 2022 7:00 pm Australia/Sydney

In 2019, MSD’s KEYTRUDA® (pembrolizumab)1 plus Eisai’s LENVIMA® (lenvatinib)2 was fast-tracked in Australia based on early clinical data under the Australian Government’s commitment to streamline processes by collaborating with overseas regulators.

This immuno-oncology combination therapy has now received final approval – and is listed on the Australian Register of Therapeutic Goods (ARTG) as a treatment option for a kind of uterine cancer called endometrial carcinoma, if laboratory tests show the cancer is not microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) and other treatments have not helped stop the disease.1,2

Since 1971, almost 50 years, only two drugs have been approved for endometrial cancer in comparison with approximately 50 for breast cancer.3,4 This treatment, the first combination of immunotherapy and a tyrosine kinase inhibitor for Australian patients with advanced or recurrent endometrial carcinoma, provides a precision treatment option for eligible patients.

Endometrial cancer is the most diagnosed gynaecological cancer in Australia – followed by ovarian and cervical cancer.5 In 2021, it is estimated that more than 3,200 new cases of endometrial cancer were diagnosed (approximately 8 women every day), and an estimated 660 women died from the disease.6 It is most common in women over 60 and in post-menopausal women.5,7

Whilst the chances of surviving for at least five years after uterine cancer diagnosis (of which approximately 95% are endometrial cancer) in Australia is 84%,6 fewer than 1 in 5 women with advanced endometrial cancer will survive 5 years or longer after the cancer is found.5

Dr Sally Baron-Hay, Medical Oncologist, Royal North Shore Hospital says, “Women with advanced endometrial cancer, the commonest diagnosed gynae oncological cancer in Australian have had limited therapeutic options until now and have faced high mortality rates. This approval is a significant step forward in the management of this cancer,” she added.

Currently, there are no screening tests or exams to find endometrial cancer early in women who are at risk, and whilst improved diet and exercise could help to lower the risk, there is no simple method to prevent women from developing this cancer.3,8

Women who have had endometrial cancer may experience physical (fatigue, changes to physical function, pain) and emotional (fear, anxiety, depression) effects from endometrial cancer and its treatment.9 The primary treatment of early-stage endometrial cancer is surgery, but it is not without considerable morbidity, especially in an increasingly ageing population.10

Dr John Bower, Medical Director and Head of Market Access, Eisai, Australia & New Zealand says, “We are very pleased that LENVIMA in combination with KEYTRUDA is now registered for eligible Australian women who have this type of advanced cancer that has progressed following previous treatment and who cannot have surgery or radiation. This has been an area of unmet need for some time, and we are looking forward to pursuing reimbursement for this group of patients.”

Prashant Nikam, Managing Director, MSD Australia & New Zealand, says, “Until now there have been limited options for women who are diagnosed at an advanced stage or find their disease has returned. Eligible Australians are now among the first in the world to have access to this combination therapy.

About KEYTRUDA1 Endometrial carcinoma indication: KEYTRUDA (pembrolizumab), in combination with LENVIMA® (lenvatinib), is indicated for the treatment of patients with advanced endometrial carcinoma that is not MSI-H or dMMR, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.1

Precautions: Immune-mediated adverse reactions, including severe and fatal cases, have occurred in patients receiving KEYTRUDA. These have included, but not limited to: pneumonitis, colitis, hepatitis, hepatoxicity (in combination with axitinib), nephritis, endocrinopathies (adrenal insufficiency, hypophysitis, type 1 diabetes mellitus, hyperthyroidism, hypothyroidism, thyroiditis), uveitis, myositis, Guillain-Barre syndrome, myasthenic syndrome/myasthenia gravis (incl. exacerbation), myelitis, vasculitis, pancreatitis, sarcoidosis, encephalitis, myocarditis, pericarditis and pericardial effusion, peripheral neuropathy, sclerosing cholangitis, solid organ transplant rejection, severe skin reactions (SJS, TEN and bullous pemphigoid), severe infusion reactions (hypersensitivity, anaphylaxis) and complications of allogeneic HSCT. Monitor thyroid and liver function. Immune-related adverse reactions have occurred after discontinuation of treatment with KEYTRUDA, can affect an estimated more than one body system and can occur simultaneously. Adverse events: In patients with endometrial carcinoma treated with KEYTRUDA/LENVIMA, the following adverse events occurred at a rate >20% and at a rate higher than doxorubicin or paclitaxel were: hypothyroidism (67% vs 0.9%), hypertension (67% vs 6%), haemorrhagic events (25% vs 15%), fatigue (58% vs 54%), diarrhoea (55% vs 20%), nausea (49% vs 47%), vomiting (37% vs 21%), stomatitis (35% vs 26%), abdominal pain (34% vs 21%), constipation (27% vs 25%), musculoskeletal disorders (53% vs 27%), decreased appetite (44% vs 21%), weight loss (34% vs 6%), proteinuria (29% vs 3.4%), urinary tract infection (31% vs 13%) , headache (26% vs 9%), dysphonia (22% vs 0.6%), palmar-plantar erythrodysesthesia (23% vs 0.9%) and rash (20% vs 4.9%). Fatal adverse events have occurred. Contraindications: None.

Refer to the Consumer Medicine Information or your doctor or pharmacist for further information about KEYTRUDA.

About LENVIMA2 Endometrial cancer indication: Lenvima, in combination with pembrolizumab, is indicated for the treatment of patients with advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.2

Lenvima® (lenvatinib mesilate) 4mg and 10 mg hard capsules.12 Lenvima is used to treat liver cancer and thyroid cancer in adults when radioactive iodine treatment has not helped stop your disease.  It is also use in combination with everolimus to treat patients with advanced kidney cancer where other treatments have not helped stop the disease and in combination with pembrolizumab to treat a kind of uterine cancer called endometrial carcinoma, if laboratory tests show the cancer is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) and other treatments have not helped stop the disease. Lenvima should not be taken if you have an allergy to lenvatinib, the active ingredient or to any of the other ingredients listed in the Consumer Medicine Information (CMI).Check with your doctor if you have high blood pressure; have a history of heart problems or stroke; are over 65 years of age; need to have or have had recent surgery or radiotherapy; have liver or kidney problems; have or have had pain in the mouth, numbness or a feeling of heaviness in the jaw, or loosening of a tooth; are receiving or have received some medicines used to treat osteoporosis or cancer; belong to an ethnic group other than white or Asian, weigh less than 60 kg; have a history of abnormal passageways (known as fistula). Very common side effects include high or low blood pressure; loss of appetite or weight loss, feeling sick and being sick, constipation, diarrhoea, stomach pain, indigestion; feeling sleepy (drowsiness or somnolence); feeling weak; cough or hoarse voice; swelling of the legs; rash; dry, sore or inflamed mouth, odd taste sensation; swelling and inflammation of the joints, and stiff muscles, bones and joints; feeling dizzy; hair loss; bleeding (most commonly nose bleeds); trouble sleeping; increased protein in the urine; urinary infections; pain (muscle, joint, headache, back); redness, soreness and swelling of the skin on the hands and feet; underactive thyroid (tiredness, weight gain, constipation, feeling cold, dry skin); low levels of sodium, potassium and calcium in blood tests; high levels of cholesterol and thyroid stimulating hormone in blood tests; decreases in the number of white blood cells; bruising and difficulty wound healing. Lenvima has risks and benefits.  Use strictly as directed.

For more information on Lenvima including side effects see the Consumer Medicine Information or speak with your doctor.

PBS information:
This combination is not listed on the Pharmaceutical Benefits Scheme (PBS) for endometrial carcinoma.

About the Merck and Eisai Strategic Collaboration. In March 2018, Eisai and Merck, known as MSD outside the United States and Canada, through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialisation of LENVIMA. Under the agreement, the companies will jointly develop, manufacture, and commercialize LENVIMA, both as monotherapy and in combination with Merck’s anti-PD-1 therapy KEYTRUDA. In addition to ongoing clinical studies evaluating the KEYTRUDA plus LENVIMA combination across several different tumour types, the companies have jointly initiated new clinical studies through the LEAP (lenvatinib and pembrolizumab) clinical program and are evaluating the combination in more than 10 different tumour types across more than 20 clinical trials.

  1. KEYTRUDA Product Information. Accessed February 2022
  2. LENVIMA Product Information. Accessed February 2022.
  3. QIMR Berghofer Medical Research Institute. Endometrial Cancer Accessed February 2022
  4. Makker, V., Green, A.K., Wenham, R.M. et al. New therapies for advanced, recurrent, and metastatic endometrial cancers. gynaecol oncol res pract 4, 19 (2017).
  5. Australian Institute of Health and Welfare (AIHW).Gynaecological Cancers in Australia – An Overview. Accessed February 2022
  6. Australian Government. Cancer Australia. Uterine Cancer Statistics. Accessed February 2022
  7. American Cancer Society. Endometrial Cancer. Accessed February 2022
  8. Onstad, Michaela A et al. “Addressing the Role of Obesity in Endometrial Cancer Risk, Prevention, and Treatment.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology vol. 34,35 (2016): 4225-4230. doi:10.1200/JCO.2016.69.4638
  9. Peter MacCallum Cancer Centre. ACSC Factsheet Endometrial Cancer. Accessed February 2022
  10. Njoku, K. et al. 2020, Best Practice & Research Clinical Obstetrics & Gynaecology, ‘Endometrial cancer prevention in high-risk women’, vol. 65, pg. 66 – 78,
  11. Australian Gynaecological Cancer Foundation. Uterine Cancers. Accessed February 2022
  12. LENVIMA Consumer Medicine Information. Accessed February 2022