What do I get with a subscription to OBR intel that I don’t already get with OBR daily?
OBR intel includes 7 main resources not available with the free OBR daily subscription service:
1. OBR Finance – our listing of oncology focused companies including streaming stock quotes and corporate profiles of the companies. Also included in OBR finance are financial indicators such as the OBR index, Cancer Patient Volume and Cancer Drug Dollar Volume (indicators brought to us by our partner IntrinsiQ), Top 5 Winners/Losers, and OBR Bulls and Bears.
2. Pipeline Online – this database of experimental oncology pipeline products is updated regularly, but the real value in Pipeline Online is that it is user friendly, meaning that you can search by tumor type, class, company, or product.
3. OBR Radar – this is our database of upcoming pivotal events in the oncology industry. In OBR Radar we include things like PDUFA dates, ODAC dates, expected Phase III clinical trial results, and anticipated approval dates. OBR Radar allows you to look forward at the events changing clinical practice and thus impacting on market dynamics.
4. Editorial Board Commentary – We have created an editorial board of world-renown oncologists that read OBR daily every day and provide their valuable insights as to how they interpret the news seen in OBR daily. You can view our current editorial board members here: http://www.obroncology.com/editorialboard/. We call it virtual access – being able to view the insights/analysis of our editorial board on the daily oncology news you see in OBR daily.
5. Pub Scan – We monitor 7 peer-reviewed oncology journals and provide you with excerpts and urls – according to your preferences – so you are up to date on the latest publications in your area of interest.
6. Access to the OBR intel dashboard where you can set your preferences, access our databases, and research historical news and publications in your specialty.
7. Plus you get to customize your daily news
But I love OBR daily and don’t want to lose it…
As a subscriber to OBR intel you still get a daily email from us. You don’t lose anything with OBR intel, in fact you get the same great content plus much more as described above.
So my daily email from OBR intel looks just like my current OBR daily?
Yes, except we’ve added:
1) a section so you get your customized news first and
2) a pub-scan section reviewing recent publications in peer-reviewed journals
Comparatively, it looks like this:
And how do I access these other resources?
Right there in OBR intel. The right hand column has links to all the OBR resources, including as much of the physician comments we could fit.
That is our push, but you can also access all the information in your OBR intel dashboard. This is where you set your preferences and access your widgets. Resources in the OBR dashboard include:
• Current and archived publications by interest area
• Current and archived news articles by interest area
• OBR Finance, OBR Radar, and Pipeline Online widgets
• OBR green
• Current and archived physician commentary
Quick, tell me why I need these other resources listed above?
Maybe you do, maybe you don’t. Depends on your role. But we call it OBR intel because there are most likely times when you want understand more about the drivers in this dynamic industry. Financial indicators tell of the health of the oncology industry, the pipeline is always interesting to review, OBR Radar is fun to review to see what’s coming, and our editorial board commentary offers unparalleled perspective.
OK, you convinced me. How does your price for a subscription compare to others?
As you know if you work in oncology, pricing is about value. We feel that given all the resources you’re gaining from a subscription to OBR intel, the value is there. We are charging $930 for an annual subscription, but we can also discuss bulk subscriptions for your company too.
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by Don Sharpe
By Tatiana Spicakova, PhD – Associate Consultant, CancerMPact®, Head of Emerging Technologies, Kantar Health
Targeted therapy has revolutionized the way cancer is treated and manufacturers continue to invest substantial resources in the development of new technologies, of which phosphoinositide-3 kinase (PI3Ks) inhibitors, either alone or in combination with MEK inhibitors, appear as the most promising next wave of targeted therapeutics.
Aberrant PI3K signaling has a known role in carcinogenesis, caused by several mechanisms such as activation of the upstream receptor tyrosine kinase, overexpression or mutational activation of PI3K, or mutational inactivation or loss of phosphatase and tensin homolog (PTEN, a negative regulator of PI3K). Given the importance of activated PI3K signaling in cancer, Class I PI3Ks are currently one of the hottest drug targets in oncology, with several small molecules in early stages of clinical development.
Given the number of PI3K inhibitors entering the clinic, selecting the right therapeutic area will be key for companies to ensure successful market entry. Preclinical data provide some guidance as to which tumor types might be sensitive to PI3K inhibition. For example, preclinical models suggest that breast tumors harboring HER2 amplifications require PI3K signaling after acquiring resistance to anti-HER2 therapies. Hence, a combination of PI3K inhibitors with Herceptin® (trastuzumab, Roche) may result in an effective therapy in this patient population. Recognizing the opportunity for PI3K inhibitors in breast cancer, several companies have initiated clinical trials in this tumor type: XL147 (Exelixis/sanofi-aventis) is in a Phase I/II trial in combination with Herceptin or Herceptin plus paclitaxel; GDC-0941 (Genentech/Roche) is in Phase I trial in combination with trastuzumab-DM1 (an antibody-drug conjugate) and in combination with paclitaxel and Avastin® (bevacizumab, Genentech/Roche); and BKM120 (Novartis) is in Phase I/II trial in combination with Herceptin and a Phase I trial combined with BEZ235 (Novartis) and paclitaxel with or without Herceptin.
Non-Small Cell Lung Cancer (NSCLC) is also likely to emerge as a therapeutic area of interest for PI3K inhibitors. It was previously shown that NSCLC tumors can become resistant to EGFR-targeted inhibitors via activation of or maintaining downstream PI3K signaling. Hence, these tumors represent an attractive opportunity for PI3K inhibitors either following progression on EGFR-targeted agents or in combination with EGFR-targeted agents in earlier settings. Not wasting any time, Genentech/Roche initiated a Phase I trial to evaluate GDC0941 in combination with Tarceva® (erlotinib, OSI/Astellas/Genentech/Roche) in NSCLC patients previously treated with chemotherapy, and Exelixis initiated Phase I trials to evaluate XL147 or XL765 in combination with Tarceva in NSCLC patients previously treated with Tarceva or Iressa® (gefitinib, AstraZeneca). Determined to lead the race, Novartis plans to open a Phase II trial to evaluate BKM120 in metastatic NSCLC with activated PI3K pathway. Unlike XL147, the drug will not be used in combination with Tarceva; instead, patients with squamous histology will either receive BKM120 or docetaxel, and patients with non-squamous histology will receive either BKM120 or docetaxel or Alimta® (pemetrexed, Eli Lilly).
Selection of other tumor types will likely depend on whether the tumors are known to harbor PI3K mutations/amplifications or PTEN mutations/deletions such as endometrial or brain tumors. Comprehensive mutational analysis of tumors from patients enrolled in PI3K inhibitor clinical trials and stratification by mutation status will be key in teasing out which genetic abnormalities are most likely to result in meaningful clinical outcomes.
Although the majority of PI3K inhibitors are under development in solid tumors, hematological malignancies also represent a therapeutic area of interest, especially for isoform-specific PI3K inhibitors. For example, constitutive activation of PI3K signaling pathway is commonly found in acute myeloid leukemia (AML), with the p110d isoform always expressed. In acute promyelocytic leukemia (APL), both p110d and p110b isoforms are expressed. Interestingly, activating mutations in the p110a catalytic subunit – that are commonly present in solid tumors – have not yet been identified in AML. Given the importance of p110d and p110b isoforms in hematological malignancies, p110d isoform specific inhibitors such as AMG319 (Amgen) and CAL101 (renamed as GS1101 following acquisition of Calistoga Pharmaceuticals by Gilead Sciences) could potentially have efficacy and safety advantages over pan-PI3K inhibitors. Acting on the evidence for the role of PI3K in hematological malignancies, Amgen plans to evaluate AMG319 in a Phase I trial in relapsed/refractory lymphoid malignancies, with the expansion cohort enrolling patients with chronic lymphocytic leukemia (CLL).
Calistoga Pharmaceuticals, acquired by Gilead Sciences earlier this year, is so far leading the race of isoform-specific PI3K development with several clinical trials ongoing in hematological malignancies. Calistoga initiated the clinical development of CAL-101 in relapsed/refractory hematological malignancies, and currently offers patients who are deriving benefit with CAL-101 the opportunity to continue treatment. Following Calistoga’s acquisition, Gilead appears to fully support the development of CAL-101 in hematological malignancies. A Phase I trial is evaluating the compound in combination with chemotherapy and CD20-targeted antibody in relapsed/refractory indolent B-cell non-Hodgkin’s lymphoma (NHL) or CLL; a different Phase I trial is evaluating CAL-101 monotherapy in previously untreated low-grade lymphoma; a Phase II trial is evaluating CAL-101 in combination with Rituxan® (MabThera® in Western Europe, rituximab, Biogen Idec/Genentech/Roche) in elderly patients with previously untreated CLL or small lymphocytic lymphoma (SLL), and a Phase II trial is evaluating CAL-101 in indolent B-cell NHL. Calistoga was also developing CAL-120, a dual inhibitor of p110d and p110b, which was expected to enter Phase I development in solid tumors based on the emerging role of p110b isoform in PTEN null tumors, but following the acquisition, it has not been disclosed whether Gilead still plans on taking CAL-120 into clinical development.
The excitement surrounding PI3K inhibitors was certainly evident at this year’s ASCO where data from early clinical development were presented for all 3 categories of PI3K inhibitors: (1) pan-PI3K inhibitors that target all p110 isoforms; (2) isoform-specific PI3K inhibitors that target a specific p110 isoform; and (3) PI3K/mTOR dual inhibitors that inhibit all p110 isoforms as well as mTOR.
To learn more about the presented safety and preliminary efficacy data, please refer to the full article in the July issue of OBR green.
By now you’ve seen post-ASCO QuickPolls in melanoma and GU cancers, and in between we ran a blog on some recent compelling clinical news in NSCLC. Following up on the NSCLC news, we think it is a good time to present QuickPoll outcomes in NSCLC. QuickPolls are a first glimpse into physicians’ reactions to new data presented at ASCO ’11. OBR and MDoutlook are pleased to share results from MDoutlook’s 4th annual post-ASCO survey fielded among its global network of 52,000 cancer physicians.
Quick Poll Methodology and Respondents’ Geographic Distribution
1) NSCLC Treaters Plan Increased Usage of Erlotinib While Decreasing Usage of Platinum Based Chemotherapy
2) Large Proportion of Clinicians Plan to Always Use Crizotinib EML4-ALK+ NSCLC patients
3) Anti-c-Met Combination Therapy is Expected to Have a Positive Impact on Treatment of c-Met+ Patients
4) Screening of NSCLC Patients for c-Met Mutation is Expected to Increase Dramatically in the Near Future
Quick polls are a fast way of measuring expected acceptance of clinical data post major medical meetings, and perhaps can be used to make some assumptions about adoption amongst providers. In today’s information hungry environment, the speed at which these polls can be conducted and analyzed can be advantageous for market planning and “pressure testing” acceptance of data amongst key stakeholders.
It was a big week in lung cancer with the International Association for the Study of Lung Cancer (IASLC) meeting and two new studies on lung cancer prevention and detection that caught the attention of oncologists this week. One study focused on reducing the incidence of the disease in high-risk individuals, while the other study sought to detect tumors at early stages.
Lung Cancer Prevention with Celecoxib in Former Smokers
Celecoxib [Celebrex; Pfizer] continues to show a favorable response in bronchial Ki-67 expression suggesting its efficacy for lung cancer chemoprevention. Results from a study conducted by Jenny T. Mao, MD, of the New Mexico VA Health Care System/University of New Mexico and colleagues are published in this month’s July issue of Cancer Prevention Research.
“Former smokers with high baseline Ki-67 labeling index likely have a stronger driving force of cancerization in their lungs,” said Dr. Mao in an interview. The bronchial Ki-67 labeling index after 6 months of treatment was the primary endpoint as Ki-67 expression is a marker of cellular proliferation.
The cyclooxygenase-2 (COX-2)/prostaglandin E2 pathway is known to play a pivotal role in carcinogenesis, thus inhibiting COX-2 may help to prevent lung cancer.
The 137 participants in this phase 2b, randomized, double-blind, placebo-controlled study were former smokers who had smoked at least 30 pack-years; quit and abstained from smoking for at least 1 year; had no evidence of major cardiovascular, renal, or hepatic abnormalities; and successfully completed bronchoscopy without evidence of cancer or other important findings. Participants were randomized in a 1:1 ratio to receive 6 months of celecoxib (400 mg orally twice each day) or placebo.
Celecoxib decreased the bronchial Ki-67 labeling index by an average of 34% after 6 months of treatment, while placebo increased the Ki-67 labeling index by 3.8%.
Celecoxib was associated with reduced or resolved CT-detected lung nodules. “Oral celecoxib is biologically active in both the central and peripheral respiratory epithelium. This is the first time the improvement of a central bronchial biomarker in response to a lung cancer chemopreventive agent has been linked to the favorable modulation of potential precursor lesions in the lungs,” said Dr. Mao.
Responders to celecoxib could be predicted by their baseline COX-2/15-PGDH ratio, which was 2.9-fold higher than the ratio in nonresponders. Dr. Mao stated, “This is the first study to demonstrate that the expression of key enzymes for a molecular target may help predict an individual’s responsiveness to a lung chemopreventive agent. These findings will help guide the development of a more focused, personalized approach and improve the selection of individuals that will more likely benefit in future lung cancer chemoprevention trials with celecoxib.”
This study was supported by the National Cancer Institute, and Pfizer Inc. supported study drugs and plasma celecoxib measurements.
Low-Dose CT Screening Reduces Lung Cancer Mortality
According to research published June 29 in the New England Journal of Medicine by the National Lung Screening Trial Research Team, mortality from lung cancer showed a 20% relative reduction when screening with low-dose helical computed tomography was compared with screening by chest radiography.
The 53,454 study participants were between the ages of 55 and 74 years old, had a cigarette smoking history of at least 30 pack-years, and, if they had quit smoking, they had done so within the last 15 years. Participants were randomized to be screened by low-dose CT or by single-view posteroanterior chest radiography, and then were screened 3 times at 1-year follow-up intervals.
Mortality rates in the low-dose CT group due to lung cancer showed 247 deaths per 100,000 participants compared with 309 deaths per 100,000 in the radiography group.
“The findings show that CT screening reduces lung cancer mortality by 20 percent when compared with chest x-ray, giving physicians and patients better information than before on which to base their conversations about lung cancer screening. This study was very well designed in order to eliminate many of the weaknesses that affected other such studies,” explained Albert Rizzo, MD, American Lung Association Board Chair-Elect and a pulmonary and critical care physician.
The rate of positive tests in all 3 rounds of screening was higher in the low-dose CT group, with 39% of the low-dose CT group and 16% of the radiography group having at least one positive screening result. The positive results were false positives for 96.4% of those in the low-dose CT group and 94.5% of those in the radiography group.
“Questions remain about the cost effectiveness of screening, the amount of over-diagnosis in the study, whether populations with different risk profiles benefit from screening and how the results will translate to community settings,” said Dr. Rizzo. He stated that more research is needed to see the benefit in the community.
This trial was funded by the National Cancer Institute.
by Kathy Boltz, PhD