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
Novartis has 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 inhibitor1,2,3 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-21,6
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.
For more information, please visit www.novartis.co.uk.
* Ribociclib is not indicated for concomitant use with tamoxifen.
References
1 Hortobagyi, et al. Overall survival (OS) results from the phase III MONALEESA (ML)-2 trial of postmenopausal patients with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2−) advanced breast cancer (ABC) treated with endocrine therapy (ET) ± ribociclib [Title]. Presented at the European Society of Medical Oncology (ESMO) Congress, September 16-21, 2021, (LBA17 Abstract).
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
4 Novartis Data on File. Novartis Pharmaceuticals Corp: 2021.
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
6 Hortobagyi G, Stemmer S, Burris H, et al. Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer. Annals of Oncology 29: 1541–1547, 2018
7 NHS Choices (2019). Overview – Breast cancer in women. [online] NHS. Available from: https://www.nhs.uk/conditions/breast-cancer/. [Accessed September 2021].
8 Cancer Research UK [Online]. Breast cancer incidence (invasive) statistics. Available from: http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/breast-cancer#heading-Zero [Accessed September 2021].
9 O’Shaughnessy J. Extending survival with chemotherapy in metastatic breast cancer. The Oncologist. October 2005, 10(suppl.): 20-29.
10 Cancer Research UK [Online]. Breast cancer survival statistics. Available from: http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/breast-cancer#heading-Three [Accessed September 2021]
11 ONS. Cancer survival in England – adults diagnosed 2013-2017. https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/datasets/cancersurvivalratescancersurvivalinenglandadultsdiagnosed [Accessed September 2021]
12 Sartor O, J. de Bono KN, Chi K, et al Lutetium-177–PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. NEJM 2021; doi: 10.1056/NEJMoa2107322
