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Novartis will showcase the clinical progress of multiple marketed and pipeline compounds with 160 abstracts at the 48th Annual Meeting of the American Society of Clinical Oncology (ASCO; June 1-5, Chicago).
These studies demonstrate key findings for Novartis compounds to address unmet treatment needs of patients with cancer and rare diseases.
“Among the data we will share at this year’s ASCO are results from our key products, Afinitor and Tasigna, which demonstrate the magnitude of benefit these treatments may provide for patients with some types of advanced breast cancer and chronic myeloid leukemia,” said Hervé Hoppenot, President, Novartis Oncology.
“In addition, we are seeing promising data from our early pipeline across multiple disease areas, including non-small cell lung cancer, multiple myeloma, NRAS-mutated melanoma and other solid tumors.”
Updated data from BOLERO-2
An 18-month analysis from the Phase III BOLERO-2 study (Breast cancer trials of OraL EveROlimus) (abstract #559; June 2, 8:00AM – 12:00PM) confirm that Afinitor® (everolimus) plus exemestane, an aromatase inhibitor, more than doubled the time postmenopausal women with hormone receptor-positive (HR+) advanced breast cancer lived without tumour growth (progression-free survival; PFS).
The updated results show median PFS for everolimus plus exemestane was 7.8 months compared with 3.2 months with hormonal therapy alone (hazard ratio=0.45 [95% confidence interval (CI): 0.36 to 0.54]; p<0.0001) by local investigator assessment and significantly reduced the risk of cancer progression by 55% versus exemestane alone.
In addition, 32.2% of patients in the exemestane-only arm and 25.4% in the everolimus plus exemestane arm died. The overall survival data is not yet mature.
The most common adverse events in the everolimus arm (incidence >= 30%) were stomatitis, rash, fatigue, nausea, diarrhea and decreased appetite.
The most common grade 3/4 adverse reactions (incidence >= 2%) were stomatitis, hyperglycaemia, non-infectious pneumonitis, fatigue and diarrhea.
These results are supportive of previously presented data from BOLERO-2. Regulatory submissions for Afinitor in HR+ advanced breast cancer are currently under consideration with the US Food and Drug Administration and other health authorities worldwide.
Tasigna in Philadelphia chromosome-positive CML in chronic phase
Also featured at ASCO will be two Phase III studies from the ENEST (Evaluating Nilotinib Efficacy and Safety in Clinical Trials) clinical research program, which demonstrate that twice as many adult patients with Philadelphia chromosome-positive chronic myeloid leukaemia (Ph+ CML) in chronic phase treated with Tasigna® (nilotinib) achieved deeper levels of response compared to those treated with imatinib.
These findings were first presented at the 2011 American Society of Hematology Annual Meeting and include:
· ENESTnd 36-month update showed the superiority of Tasigna vs. imatinib for the treatment of patients with newly diagnosed chronic phase Ph+ CML, with 32% of patients reaching the deepest levels of response on Tasigna compared to 15% on imatinib(abstract #6509; June 1, 1:00PM – 5:00PM)[2].
· ENESTcmr 12-month analysis demonstrated that switching patients with detectable Bcr-Abl transcripts from imatinib to Tasigna resulted in deeper molecular responses compared to those patients who remained on imatinib, with 23% of patients switched to Tasigna achieving undetectable levels of Bcr-Abl compared to 11% who continued on imatinib (abstract #6505; June 4, 9:30AM – 9:45AM)[3].
These data will also be presented at 17th Congress of the European Haematology Association (EHA), June 14-17 in Amsterdam.
Notable data on Novartis pipeline compounds
Early data on several Novartis pipeline compounds show promise for further research and development in areas of unmet medical needs and for targeted treatment approaches.
“Our strong pipeline data demonstrate the progress we are making to target new signalling pathways, including MEK, ALK, Hh and PI3K, that play a critical role in many types of cancers where there remain significant unmet medical needs,” said Alessandro Riva, Global Head, Oncology Development & Medical Affairs, Novartis Oncology. “This is representative of our ongoing research using multiple strategies across a broad range of cancers and rare diseases.”
- BEZ235 – Phase I/Ib dose-escalation study of BEZ235 plus trastuzumab in patients with trastuzumab-resistant HER2+ metastatic breast cancer demonstrated an acceptable safety profile and established maximum tolerated dose(abstract #508; June 2, 1:30PM – 1:45PM)[5].
- BKM120 – Phase Ib study of BKM120 with letrozolein patients with metastatic ER+/HER2- breast cancer (abstract #510; June 2, 2:15PM – 2:30PM)[6] and a Phase Ib study of BKM120 in combination with the MEK inhibitor GSK1120212 in patients with advanced solid tumors showed positive safety results for these combinations. Signs of clinical activity were seen in patients with RAS/RAF-mutated tumors treated with BKM120 and GSK1120212 (abstract #3003; June 3, 10:45AM – 11:00AM)[7].
- LBH589 – Updated data from the Phase II PANORAMA-2 (PANobinostat ORAl in Multiple myelomA) study showed promise of LBH589 in combination with bortezomib and dexamethasone to achieve overall responses and clinical benefit in patients with relapsed and bortezomib-refractory multiple myeloma (abstract #8012; June 3, 9:00AM – 9:15AM).
- LDE225 – A Phase I/II study demonstrated promising efficacy of LDE225 in pediatric patients with recurrent medulloblastoma and correlative analysis supports the use of the 5-gene hedgehog (Hh) assay as a pre-selection tool in future trials (abstract #9519; June 4, 12:00PM – 12:15PM).
- LDK378 – First-in-human Phase I study of LDK378 showed preliminary clinical response in patients with ALK-positive advanced non-small cell lung cancer (abstract #3007; June 3, 12:00PM – 12:15PM).
- MEK162 – Phase II study of MEK162 showed clinical activity in patients with BRAF and NRAS-mutated advanced melanoma. This is the first targeted therapy to show activity in patients with NRAS-mutated melanoma (abstract #8511; June 4, 3:45PM – 4:00PM).
