Novartis unveils new data at ESMO 2021, including compelling longest ever reported median overall survival data in advanced breast cancer, as it continues to push the boundaries of innovation

• Data demonstrate Novartis’ unwavering commitment to reimagining cancer care for patients in the UK in advanced breast cancer and metastatic prostate cancer
• The MONALEESA-2 final analysis shows that Kisqali^®(ribociclib) is the only CDK4/6 inhibitor that has shown a statistically significant overall survival (OS) benefit^1,2,3 and the longest ever reported media overall survival with an aromatase inhibitor for postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC) in the first-line (1L) setting⁴
• New quality of life data for ¹⁷⁷Lu-PSMA-617 plus standard of care shows delay in worsening of health-related quality of life (HRQoL) and pain in heavily pre-treated patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) compared to standard of care alone⁵

 

Today Novartis announced innovative new key data in advanced breast and prostate cancer at the European Society for Medical Oncology (ESMO) Annual Meeting from its portfolio of approved and investigational therapies aimed at transforming the lives of people living with cancer.

 

The results, presented today as one of the late-breaking studies, highlights the final overall survival (OS) analysis of the Phase III MONALEESA-2 study, which evaluated Kisqali^® (ribociclib) in combination with letrozole compared to placebo plus letrozole in postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced or metastatic breast cancer with no prior systemic treatment for advanced disease.¹

 

Ribociclib in combination with letrozole met its secondary endpoint of OS, demonstrating a statistically significant and clinically meaningful improvement in survival (median 63.9 vs. 51.4 months; HR=0.76; 95% CI: 0.63-0.93; p=0.004).¹

 

Prof. David Cameron, Professor of Oncology and Director of Cancer Services, NHS Lothian at University of Edinburgh, and a member of the MONALEESA-2 steering committee, says, “The MONALEESA-2 final analysis shows a clear improvement in overall survival that is meaningful for patients.  It confirms that ribociclib is the only CDK4/6 inhibitor^1,2,3 that has shown statistically significant overall survival benefit when combined with an aromatase inhibitor and given to postmenopausal women with [HR+/HER2-] advanced breast cancer in the first-line setting. This is a significant result for women with advanced breast cancer and will hopefully provide them with more time with their family and loved ones.”

 

The analysis found that after a median follow-up of over six and a half years, the longest for any CDK4/6 inhibitor trial to date,⁴ the improvement in the median OS was over one year.¹ MONALEESA-2 showed that after five years, patients treated with ribociclib in combination with letrozole had more than a 50% chance of survival (52.3% vs. 43.9%; 95% CI: 46.5-57.7 vs. 38.3-49.4).¹ In MONALEESA-2, an exploratory analysis showed nearly a 12-month delay in time to chemotherapy with ribociclib and letrozole (median 50.6 vs. 38.9 months; HR=0.74; 95% CI: 0.61-0.91) compared to those taking letrozole alone.¹ With this longer follow-up, no new safety signals were observed; adverse events were consistent with previously reported Phase III trial results for ribociclib.

 

At the time of the second interim analysis, in MONALEESA-2, the primary endpoint progression-free survival (PFS) was met at the initial analysis 25.3 months [median PFS; 95% CI (23.0–30.3) vs. 16.0 months (95% CI 13.4–18.2) for placebo plus letrozole; (HR=0.568; 95% CI 0.457-0.704; p<0.0001).6 These new OS results mark the third statistically significant and clinically meaningful survival benefit achieved by ribociclib in combination with endocrine therapy* in the MONALEESA programme.

 

In the UK, breast cancer is the most common type of cancer, with around 55,000 women diagnosed with breast cancer each year.7^,8 Approximately 30% of women with earlier stages of breast cancer will develop advanced disease.9 Advanced breast cancer is an incurable disease, it is known that only 66% of women will survive for over a year or more and around 26.2% for five years when diagnosed at the latest stage.10,11

 

Mari Scheiffele, Novartis Oncology General Manager, UK & Ireland states, “We are very aware of the challenges faced by those living with advanced breast cancer and are reimagining how we deliver care in the UK. The innovative data show how by using our four-platform strategy we are securing meaningful advancements for patients with this disease. We know data saves lives and the deeper analysis of the statistically significant overall survival data for Kisqali is promising. It not only demonstrates our bold patient-first approach and ongoing commitment to the breast cancer community, but continued alignment to the priorities for the NHS in its Long-Term Plan for cancer patients. We continue to partner with the NHS and the entire health ecosystem to identify and implement solutions for these patients, no matter where they are or what their background.”

 

Another key highlight of the data presented at ESMO is the quality-of-life data for the Phase III VISION study evaluating ¹⁷⁷Lu-PSMA-617, an investigational targeted radioligand therapy for heavily pre-treated patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) plus standard of care for mCRPC versus standard of care alone. These data show delay in worsening of health-related quality of life (HRQoL) and pain in heavily pre-treated patients with PSMA-positive mCRPC compared to standard of care alone.⁵

 

Alessandra Dorigo, General Manager UK, Ireland, Baltics and Nordics in Novartis Advanced Accelerator Applications (AAA) comments, “Quality of life is one of the most important measures to look at in advanced prostate cancer. Many patients living with metastatic castration-resistant prostate cancer (mCRPC) experience reduced physical functioning as well as significant pain. The data from the Phase III VISION study of a radioligand therapy in this advanced prostate cancer setting confirm the potential of ¹⁷⁷Lu-PSMA-617 to support better quality of life outcomes for people living with mCRPC. I believe we are driving forward genuine advances in prostate cancer where we know there is a great need for innovative treatment options that do not detrimentally impact a patients’ quality of life. We have a bold ambition to improve patient outcomes and are very excited about what we can achieve for these patients in the UK and beyond.”

 

About MONALEESA-2^1,6

MONALEESA-2 was a N=668, double-blind, placebo-controlled, 1:1 randomisation, multicentre, phase III trial in postmenopausal women with HR+/HER2- aBC. As 1L in advanced disease. No prior endocrine therapy for aBC and no previous systemic chemotherapy for advanced disease. ribociclib 600 mg or placebo orally once daily (3 weeks on/1 week off) + letrozole 2.5 mg continuous. The primary endpoint was locally assessed PFS and the key secondary endpoint was OS. Other secondary endpoints included the overall response rate the clinical benefit rate, safety, and quality-of-life assessments.

 

About Phase III VISION

VISION is an international, prospective, randomized, open-label, multicenter, phase III study to assess the efficacy and safety of ¹⁷⁷Lu-PSMA-617 (7.4 GBq administered by intravenous infusion every 6 weeks for a maximum of 6 cycles) plus investigator-chosen standard of care in the investigational arm, versus standard of care in the control arm.¹² Patients with PSMA PET-scan positive mCRPC, and progression after prior taxane and androgen receptor pathway inhibitors, were randomized in a 2:1 ratio in favor of the investigational arm.¹² The study met both alternate primary endpoints of radiographic progression free survival and overall survival; secondary endpoints were also met.¹²

 

Novartis has over 30 years of heritage in oncology, spanning back to the approval of the first targeted therapy and beyond, transforming the lives of people living with cancer and life-threatening blood disorders. Novartis’ bold ambition is grounded in its industry-leading oncology and haematology pipeline of more than 45 different compounds across 70+ development programmes. Novartis is at the forefront of medicines development. It has been the number one commercial sponsor of UK clinical trials over the past ten years and believe it is their responsibility to continue to move at pace and deliver innovations that are laser-focused on unmet patient need and the requirements of health systems.

About Kisqali^® (ribociclib)¹³

Kisqali^® (ribociclib) is a selective cyclin-dependent kinase inhibitor, a class of drugs that help slow the progression of cancer by inhibiting two proteins called cyclin-dependent kinase 4 and 6 (CDK4/6). These proteins, when over-activated, can enable cancer cells to grow and divide rapidly. Targeting CDK4/6 with enhanced precision may play a role in ensuring that cancer cells do not continue to replicate uncontrollably.

 

Ribociclib is approved for use in the UK for the treatment of women with HR+/HER2- locally advanced or metastatic breast cancer in combination with an aromatase inhibitor or fulvestrant as initial endocrine-based therapy, or in women who have received prior endocrine therapy. In pre- or perimenopausal women, the endocrine therapy should be combined with a luteinising hormone-releasing hormone (LHRH) agonist.

 

Ribociclib can be taken with or without food as a once-daily oral dose of 600 mg (three 200 mg tablets) for three weeks, followed by one week off treatment. Ribociclib is taken in combination with four weeks of any non-steroidal aromatase inhibitor, or with 500 mg of fulvestrant that should be given by intramuscular injection on Days 1, 15, 29, and once monthly thereafter. Please refer to the SmPC of ribociclib for additional details.

 

Important Safety Information from the Kisqali EU SmPC¹³

Kisqali® (ribociclib) is a prescription medicine approved in combination with an aromatase inhibitor as initial endocrine - based therapy in women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer or fulvestrant as initial endocrine - based therapy or following disease progression on endocrine therapy in postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer. It is not known if Kisqali is safe and effective in children or adolescents. Kisqali can cause a heart problem known as QT prolongation. This condition can cause an abnormal heartbeat and may lead to death. Kisqali is not indicated for concomitant use with tamoxifen due to an increased risk of QT prolongation. Patients should tell their health care provider right away if they have a change in their heartbeat (a fast or irregular heartbeat), or if they feel dizzy or faint. Kisqali can cause serious liver problems. Patients should tell their health care provider right away if they get any of the following signs and symptoms of liver problems: yellowing of the skin or the whites of the eyes (jaundice), dark or brown (tea-colored) urine, feeling very tired, loss of appetite, pain on the upper right side of the stomach area (abdomen), and bleeding or bruising more easily than normal. Low white blood cell counts are very common when taking Kisqali and may result in infections that may be severe. Patients should tell their health care provider right away if they have signs and symptoms of low white blood cell counts or infections such as fever and chills. Before taking Kisqali, patients should tell their health care provider if they are pregnant, or plan to become pregnant as Kisqali can harm an unborn baby. Females who are able to become pregnant and who take Kisqali should use highly effective birth control during treatment and for at least 3 weeks after the last dose of Kisqali. Do not breastfeed during treatment with Kisqali and for at least 3 weeks after the last dose of Kisqali. Patients should tell their health care provider about all of the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements since they may interact with Kisqali. Patients should avoid grapefruit or grapefruit juice while taking Kisqali. The most common side effects (incidence >=20%) include infections, white blood cell count decreases, headache, cough, nausea, tiredness, diarrhoea, vomiting, constipation, hair loss and rash. The most common Grade 3/4 side effects (incidence >5%) were infections,  white blood cell count decreases, low red blood cells, abnormal liver function tests, low lymphocytes, low phosphate levels and vomiting. Abnormalities were observed in haematology and clinical chemistry laboratory tests.

 

Further information can be found in the SmPC here: https://www.medicines.org.uk/emc/product/8110#gref.   

 

About MONALEESA-2^1,6

MONALEESA-2 was a N=668, double-blind, placebo-controlled, 1:1 randomisation, multicentre, phase III trial in postmenopausal women with HR+/HER2- aBC. As 1L in advanced disease. No prior endocrine therapy for aBC and no previous systemic chemotherapy for advanced disease. ribociclib 600 mg or placebo orally once daily (3 weeks on/1 week off) + letrozole 2.5 mg continuous. The primary endpoint was locally assessed PFS and the key secondary endpoint was OS. Other secondary endpoints included the overall response rate the clinical benefit rate, safety, and quality-of-life assessments.

 

About MONALEESA-3¹⁴

MONALEESA-3 was a randomised, double-blind, placebo-controlled, multi-centre, phase III trial in postmenopausal women with HR+/HER2- mBC who received no or only 1 prior line of endocrine therapy for advanced disease, and those who had had a relapse during or within 12 months after completion of adjuvant or neoadjuvant endocrine therapy. Patients (N=726) were stratified by the presence of liver and/or lung metastases and prior endocrine therapy. Patients were randomised (2:1) to receive either KISQALI 600 mg oral (3 weeks on, 1 week off) and fulvestrant 500 mg (intramuscular injection on Days 1, 15, 29, and once monthly thereafter) or placebo (3 weeks on, 1 week off) and fulvestrant 500 mg (intramuscular injection on Days 1, 15, 29, and once monthly thereafter). The primary end point was investigator assessed progression free survival. Secondary end points included overall survival, overall response rate, clinical benefit rate, and safety.

 

About Phenotypic Precision Medicine in Advanced Prostate Cancer

Despite advances in prostate cancer care, there is a high unmet need for new targeted treatment options to improve outcomes for patients with metastatic castration-resistant prostate cancer (mCRPC). There are around 48,500 new prostate cancer cases in the UK every year, (2015-2017)¹⁵, making it the most commonly diagnosed in men cancer in the UK. The five-year survival rate for patients with mCRPC is approximately 15%.¹⁶

 

More than 80% of prostate cancer tumours highly express a phenotypic biomarker¹⁷ called Prostate Specific Membrane Antigen (PSMA)^{18,19,20,21,22} making it a promising diagnostic (through positron emission tomography (PET) scan imaging) and therapeutic target for radioligand therapy.²³

 

About ¹⁷⁷Lu-PSMA-617

¹⁷⁷Lu-PSMA-617 is an investigational PSMA-targeted radioligand therapy for metastatic prostate cancer. It is a type of precision cancer treatment combining a targeting compound (ligand) with a therapeutic radioisotope (a radioactive particle).^24,25,26 After administration into the bloodstream, ¹⁷⁷Lu-PSMA-617 binds to prostate cancer cells that express PSMA²⁷, a transmembrane protein, with high tumour-to-normal tissue uptake.^24,28,29 Once bound, emissions from the radioisotope damage tumour cells, disrupting their ability to replicate and/or triggering cell death.^30,31,32 The radiation from the radioisotope works over very short distances to limit damage to surrounding cells.^23,24,28

 

About VISION

VISION is an international, prospective, randomised, open-label, multicenter, Phase III study to assess the efficacy and safety of ¹⁷⁷Lu-PSMA-617 (7.4 GBq administered by i.v. infusion every 6 weeks for a maximum of 6 cycles) plus investigator-chosen best standard of care in the investigational arm, versus best standard of care in the control arm.¹² Patients with PSMA PET-scan positive mCRPC, and progression after prior taxane and androgen receptor- pathway inhibitors were randomised in a 2:1 ratio in favour of the investigational arm. The alternate primary endpoints were rPFS and OS.¹² The study enrolled 831 patients.

 

About Novartis 

Novartis is reimagining medicine to improve and extend people’s lives. As a leading global medicines company, we strive to use innovative science and digital technologies to create treatments in areas of great medical need. In our quest to find new medicines, we consistently rank among the world’s top companies investing in research and development. Novartis products reach more than 800 million people globally and we are finding innovative ways to expand access to our latest treatments. About 109,000 people of nearly 140 nationalities work at Novartis around the world.

 

In the UK, we employ approximately 1,500 people to serve healthcare needs across the whole of the UK, as well as supporting the global operations of Novartis. Since 2014, Novartis has invested over £200 million in R&D and is a leading sponsor of clinical trials, in the UK. For more information, please visit www.novartis.co.uk                                                                                                                               

Novartis UK is on Twitter. Sign up to follow @NovartisUK at www.twitter.com/novartisuk

References

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2 H. S. Rugo, R. S. Finn, V. Diéras et. al. Palbociclib plus letrozole as first-line therapy in estrogen receptor positive/human epidermal growth factor receptor 2-negative advanced breast cancer with extended follow-up Breast Cancer Research and Treatment (2019) 174:719–729

3 Stephen Johnston, Miguel Martin, Angelo Di Leo et. al. MONARCH 3 final PFS: a randomized study of abemaciclib as initial therapy for advanced breast cancer Breast Cancer (2019) 5:5 ; https://doi.org/10.1038/s41523-018-0097-z

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5 Novartis data on File. Abstract 3116. Health-related quality of life (HRQoL), pain and safety outcomes in the phase 3 VISION study of 177Lu-PSMA-617in patients with metastatic castration-resistant prostate cancer

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³² Ruigrok E, van Vliet N, et al. Extensive preclinical evaluation of lutetium-177-labeled PSMA-specific tracers for prostate cancer radionuclide therapy. Eur J Nucl Med Mol Imaging. 2020; 48: 1339-1350

UK | SEPTEMBER 2021 | MLR ID 151679