Introduction

In an effort to provide you with timely market feedback from ASCO 2013, OBR and MDoutlook are pleased to share results from MDoutlook’s third OncoPoll™ from the meeting exploring Ovarian and Cervical cancers.

OncoPoll™ Methodology

• Primary research phase involved a global survey to verified and validated medical oncologists and multi-disciplinary physicians with an identified clinical interest in gynecological cancers utilizing targeting parameters within the proprietary MDoutlook^® global cancer treater database
• Timing: June 2013. Launched two days after close of 2013 American Society of Clinical Oncology (ASCO) Annual Meeting, held in Chicago, IL., May 31-June 4, 2013
• Fielding via <10 minute long interactive internet survey utilizing proven effective methodology via the MDoutlook^® survey tool
• Links to discussed abstracts on the ASCO website were provided within the survey
• Reponses at data collection: 91 on June 25^th
• No financial incentives provided for participation

Geographic Distribution of Respondents

Attendance at 2013 ASCO Annual Meeting

Key Conclusions

• About half of all survey respondents attended this year’s ASCO annual meeting
• Proportionally, Ex-US respondents had slightly more attendees than US respondents
• In-line with results from previous years

US Survey Participants’ Gynecologic Cancer Patient Flow:  Average Over 27 Cases Each Month

Key Conclusions

• US survey participants* averaged nearly 15 cases of ovarian cancer last month
  • More than all other gynecologic cancers combined
  • Over half of the cases involved metastatic disease
• Four cases of cervical cancer was the average monthly volume for US participants
  • Over a third of the cervical cancers involved metastatic disease

* Survey Participants = Medical Oncologists and multi-disciplinary physicians with an identified clinical interest in gynecological cancers

Ex-US Survey Participants’ Gynecologic Cancer Patient Flow: Average Nearly 27 Cases Each Month

Key Conclusions

• Ex-US survey participants* also averaged nearly 15 cases of ovarian cancer last month
  • More than all other gynecologic cancers combined
  • Nearly two thirds of the cases involved metastatic disease
• Five cases of cervical cancer was the average monthly volume for  Ex-US participants
  • Over half of the cervical cancers involved metastatic disease

* Survey Participants = Medical Oncologists and multi-disciplinary physicians with an identified clinical interest in gynecological cancers

Dosing Schedule for 1st Line Chemotherapy for Ovarian Cancer: Improved Schedule Is Clinically Important to Oncologists

Key Conclusions

• A majority of oncologists agree that an improved 1st line chemotherapy dosing schedule for advanced ovarian cancer is important to their practice
  • ~1/3 believe this a very important information (rate as 6 or 7)
• Slightly higher ratings from Ex-US respondents

Neoadjuvant Chemotherapy for Advanced Ovarian Cancer: No Consensus as to Its Impact on Clinical Practice

Key Conclusions

• EX-US oncologists have a more favorable view of the CHORUS trial than US oncologists
• Outside of the US, over a third of oncologists think this neoadjuvant approach will become a standard of care
  • Only 1 in 8 US oncologists believe the same wide impact on clinical practice
• Few Ex-US oncologists believe the neoadjuvant approach used in the CHORUS trial will not be used in clinical practice
• 1 in 5 US oncologists think that the CHORUS trial will have little to no impact on their practice

Maintenance Therapy for Advanced Ovarian Cancer: Large Increase in Pazopanib Usage Expected

Key Conclusions

• 40 to 50% of all patients with advanced ovarian cancer are expected to receive some type of maintenance therapy
  • Represents about a doubling from current levels
  • Slightly higher proportional increase  outside of the US due to the slightly lower current usage of maintenance therapy
• A 5-fold increase in the usage of pazopanib as a maintenance therapy is expected
  • About a third of ovarian cancer patients are expected to receive maintenance therapy with pazopanib
  • Similar  changes in US and Ex-US treaters

Adding Bevacizumab to Chemotherapy for Cervical Cancer: Wide Integration into Clinical Practice; New Standard of Care in US?

Key Conclusions

• Addition of bevacizumab to chemotherapy for cervical is expected to grow by 8 fold in the US to be used in half of all patients with metastatic or recurrent / persistent disease
• Ex-US physicians anticipate adding bevacizumab to chemotherapy for 1/3 of their patients with recurrent/persistent disease or metastatic disease
• Little difference in the treatment of patients with persistent/recurrent disease or metastatic disease

Conclusions: Impact of ASCO 2013 on Clinical Practices for Gynecologic Cancers

• Ovarian cancer is the main type of gynecologic cancers seen in clinical practices
  • Oncologists’ patient flow in ovarian cancer is ~3-4x greater than cervical cancer
  • Most of oncologists’ gynecologic cancer practice involves metastatic disease, especially concerning ovarian cancer
• New information on the dosing schedule for 1st line chemotherapy for ovarian cancer is seen as important by most treaters of this cancer type and will likely be integrated into clinical practice right away
  • Few think this new data has no importance to their practice
• Splitting planned chemotherapy into a neoadjuvant and adjuvant approach for advanced ovarian cancer is widely seen as having an impact on clinical practices
  • No real consensus as to how much of an impact or for how many patients
  • Outside of the US, over a third of treaters say this will have a large impact for most patients
• A 5-fold increase in the usage of pazopanib maintenance therapy for advanced ovarian cancer is expected
  • About a third of patients will receive pazopanib in the maintenance setting
  • Overall usage of any type of maintenance therapy will double to 40-50% of these patients
  • Increases are roughly similar between those in and outside of the US, although overall levels will remain slightly higher in the US
• A large increase in the usage of bevacizumab with chemotherapy will be seen in cases of advanced cervical cancer
  • ~50% of patients in US and nearly a third of patients outside of the US will receive bevacizumab
  • Usage is expected to be mostly equal between recurrent / persistent and metastatic disease

Submitted by Jan Heybroek, President and Robert Stephan, Sr. Director Medical Services, MDoutlook

OncoPoll™ Methodology

• Primary research phase involved a global survey to verified and validated medical oncologists and multi-disciplinary physicians with an identified clinical interest in gastrointestinal cancers utilizing targeting parameters within the proprietary MDoutlook^® global cancer treater database
• Timing: June 2013. Launched three days after close of 2013 American Society of Clinical Oncology (ASCO) Annual Meeting, held in Chicago, IL., May 31-June 4, 2013
• Fielding via <10 minute long interactive internet survey utilizing proven effective methodology via the MDoutlook survey tool
• Links to discussed abstracts on the ASCO website were provided within the survey
• Reponses at data collection: 97 on June 20^th
• No financial incentives provided for participation

Geographic Distribution of Respondents

Attendance at 2013 ASCO Annual Meeting

Key Conclusions

• About half of all survey respondents attended this year’s ASCO annual meeting
• Proportionally, Ex-US respondents had slightly more attendees than US respondents
• This is in-line with results from previous years

Survey Participants’ GI Cancer Patient Flow: Average Nearly 40 Cases of GI Cancer Each Month

Key Conclusions

• Participants averaged 20-25 cases of colorectal cancer (CRC) last month
  • Ex-US participants reported  treating 21% more colorectal cancer patients than US participants
• Eight to nine cases of pancreatic cancer was the average monthly volume for survey participants
• HCC case volume was the lowest at ~ 5 cases / month
• Patient flow is roughly similar between US and Ex-US respondents

Survey Participants’ GI Cancer Patient Flow: Majority of Patients Have Metastatic Disease

Key Conclusions

• ~1/2 of the CRC and HCC patients seen by survey participants have metastatic disease
• Nearly 3/4 of the pancreatic cases involve metastatic disease
• Prevalence of metastatic disease is roughly similar between US and Ex-US respondents

FOLFIRI + Biologic as 1st Line Treatment for mCRC: Expected Significant Shift Towards Cetuximab Preference

Key Conclusions

• Increased use of cetuximab (Cetux) with FOLFIRI as 1^st line treatment for KRAS wild-type metastatic CRC is expected due to the results of the FIRE-3 trial
  • About a 40% increase in cetuximab usage is expected – Significant impact
  • ~50% of the increase comes at  the expense of bevacizumab (Bev) usage in the 1^st line
  • Ex-US respondents have and will continue to use more biologics with FOLFIRI than US respondents

Bevacizumab Usage in Maintenance Setting for mCRC: New Data Will Cause >25% of Oncologists to Increase Usage

Key Conclusions

• In the US, the majority of oncologists will not change their usage of bevacizumab in the maintenance setting due to the results from the CAIRO-3 and SAKK 41/06 trials
  • For those who will change their usage, most will increase bevacizumab usage somewhat
• Outside of the US, those who will somewhat increase usage of bevacizumab in maintenance setting is nearly equal to those who will not change their current usage
• Very few will reduce their usage due to this new information

Abraxane Usage in Metastatic Pancreatic Cancer: Expect Half of Patients to Receive Abraxane as Treatment

Key Conclusions

• Worldwide, 44% of metastatic pancreatic cancer patients are expected to receive Abraxane as treatment
  • Ex-US respondents are more aggressive in their expected increase due to lower previous levels of usage
• Due to the results of the MPACT trial, 50% of US patients with metastatic pancreatic cancer are expected to receive Abraxane as treatment
  • 22% of oncologists will use Abraxane + gemcitabine in 76-100% of their patients (data not shown)
  • Significant 2.4 fold increase in Abraxane usage is expected: 50% expected usage vs. 20% previous usage

Expectations for Regulatory Approval for Abraxane in Metastatic Pancreatic Cancer: Oncologists Believe Approval is Very Likely

Key Conclusions

• Oncologists agree with notion that Abraxane will receive regulatory approval for use in pancreatic cancer
  • 20-25% are absolutely certain of it
• Slightly higher expectations from US oncologists

2nd Line Treatment for HCC: Only a Limited Subset of Patients Receive Post-Sorafenib Treatment

Key Conclusions

• Fewer than a 1/3 of US HCC patients receive a 2^nd line treatment following sorafenib treatment
  • 20% of US oncologists will use a 2^nd line approach in a majority of their patients (data not shown)
• Only 20% of HCC patients outside of the US receive a post-sorafenib treatment
  • 6% of Ex-US oncologists will use a 2^nd line approach in a majority of their patients (data not shown)
• No consensus for 2^nd line approach, but Xeloda (capecitabine) was most commonly mentioned

Conclusions: Impact of ASCO 2013 on Clinical Practices for Gastrointestinal Cancers

• Colorectal cancers (CRC) are the main type of gastrointestinal cancers seen in clinical practices
  • Oncologists’ patient flow in CRC is ~2-3x greater than in pancreatic cancer and ~4-5x greater than in HCC
  • Most of oncologists’ gastrointestinal cancer practice involves metastatic disease, especially concerning pancreatic cancer
• In the front-line setting for mCRC, a significant increase of 40% in the usage of cetuximab in combination with FOLFIRI is expected due to the FIRE-3 results
  • ~50% of this increase will be at the expense of bevacizumab
  • FOLFIRI without either of these biologics will still be used in 30-40% of the 1^st line cases
• Some increase in the use of bevacizumab in the maintenance setting is expected due to the results of the CAIRO-3 and SAKK 41/06 trials
  • 25% (US) and 40% (Ex-US) respondents will increase their usage in this setting
  • Most or the remaining will not change their current practices due to this new information
• Abraxane is expected to be used in 50% of US patients and 44% of global patients with metastatic pancreatic cancer
  • Increased usage represents a 2.4 fold increase from current usage levels
  • Outside of the US, a 5.2 fold increase is expected (from 7%of patients to 38%)
  • Most agree with notion that Abraxane will receive regulatory approval for metastatic pancreatic cancer
• Post-sorafenib treatments for metastatic HCC are rarely used
  • More 2^nd line treatments in the US (29%) than outside of the US (20%)
  • Few try 2^nd line treatments in most of these patients

Payers are increasingly more proactive in their management of drug expenditures in cancers, such as breast cancer, non-small cell lung cancer, and colorectal cancer, where there are many therapeutic options.  As more therapeutic alternatives for advanced melanoma become available, it increases opportunities for payers to manage utilization; and it may also provide manufacturers with opportunities to define the value of their respective drugs through clinical and price differentiation.

Near-Term Management of Oral Therapies in BRAF-Mutated Melanoma

With the imminent entrance of Tafinlar (dabrafenib) and Mekinist (trametinib) to the U.S. market in the third quarter of 2013 for BRAF-mutated metastatic melanoma (approximately 40%-50% of market), GlaxoSmithKline is redefining value in this space.  Tafinlar’s labeling indicates that, like Zelboraf [vemurafenib; Plexxikon/Genentech/Roche/Daiichi-Sankyo], it is only approved for use in patients with the V600E mutation (approximately 80% of all BRAF mutations).

Price is an obvious difference between Tafinlar and Zelboraf in which payers could implement step therapy, as both drugs are relatively similar in terms of efficacy. In the U.S., the wholesale acquisition cost of Tafinlar will reportedly be $7,600 a month, which essentially undercuts Zelboraf’s approximate cost of $10,000 a month. The price difference may be partially due to Tafinlar’s later entrance to market, but may also be part of GSK’s long-term strategy for the use of Mekinist and Tafinlar in combination with each other.

Currently, Mekinist (priced at $8,700/month) has a specific limitation in its label to not be used after treatment with a BRAF V600E inhibitor. This may be enforced by payers although Mekinist has the advantage of being the only agent indicated for use in patients with the BRAF V600K mutation.

The combination of Mekinist and Tafinlar showed an improvement in progression-free survival (PFS) compared with Tafinlar alone in a Phase 2 trial.  With this early signal, GSK has initiated two Phase 3 trials (nicknamed COMBI) to confirm the results that the combination therapy is superior to Tafinlar alone or Zelboraf alone. In all likelihood the combination will move forward into clinical practice. The question is whether the combination (or even the use of Mekinist after progression with a BRAF inhibitor) will be reimbursed with an NCCN recommendation before launch in early Q3, at a later point before the COMBI trials report, or after the COMBI results.  The combination regimen would bump cost of therapy for advanced melanoma to $16,000 a month with an average duration of therapy of one year, likely spurring greater interest in payer utilization management.

Reshaping Value Propositions in Melanoma with Immunotherapy

Bristol-Myers Squibb’s immunotherapy, Yervoy (ipilimumab) was a breakthrough drug, and thus was able to be launched at a substantial price with a fixed regimen of four injections costing approximately $120,000. The most critical aspects of its value proposition is its long-term responses that lead to unprecedented long-term survival for advanced melanoma though this is accompanied by immune-related adverse events that often affect the gastrointestinal tract.

Early data suggest that BMS’s follow-up immunotherapy, nivolumab, might be more active than Yervoy and might be active in patients previously treated with Yervoy without the associated immune-related toxicities.  Also, exciting Phase 1 data suggest that the combination of these two drugs will improve long-term survival better than either agent alone.  BMS has initiated three Phase 3 trials to confirm the activity of nivolumab and the combination (nicknamed CheckMate):  nivolumab as a monotherapy in Yervoy-pretreated and Yervoy-naïve patients versus chemotherapy and a third trial comparing nivolumab and Yervoy versus the combination.

BMS will have interesting launch choices including whether to launch nivolumab with only single-agent data or with combination data.  With the superior value proposition suggested in the Phase 1 results, single-agent nivolumab would likely yield a premium price compared with Yervoy.  However, BMS might be faced with a similar issue as GSK and pricing decisions with an assumption that the combination would move forward into the clinic.

Implications

The current number of available treatments for BRAF-mutated melanoma, the emerging availabilities of immunotherapies, and their likely associated costs, suggest strong payer management in advanced melanoma may be utilized in the near future. For a disease that has garnered little attention previously, the emergence of therapies for advanced melanoma will give payers impetus to manage drug therapy.

A key clinical argument remains whether the emergence of the immunotherapies has physicians thinking that they will be used before BRAF inhibitors given the long-term survival these convey in converse to current thinking. Payers and health authorities could mandate a BRAF or MEK inhibitor over Yervoy given the biomarker significance, yet cancer-resistance against the BRAF and MEK inhibitors is inevitable, suggesting that patients with BRAF-mutated melanoma have a definite ceiling in survival without using an immunotherapy.

Unlike the BRAF and MEK inhibitors, Yervoy, a PD-1 inhibitor, does not have a biomarker. If a biomarker such as PD-1 expression can be validated for PD-1 and PD-L1 antibodies, their value proposition would be more substantial, perhaps providing a larger reason to price the drugs highly. The melanoma market has only recently been transformed, and these data and ongoing clinical development with PD-1 and PD-L1 antibodies suggest that it’s set to be transformed even further!

Melanoma treatment is likely heading toward combinations, whether it’s a BRAF/MEK combination, a BRAF inhibitor plus an immunotherapy or duel immunotherapies.  These agents will increasingly affect drug expenditures for patients and payers.  Manufacturers may need to become more creative with patient assistance programs as combination therapies push regimen prices beyond $15,000 a month. The resulting patient out-of-pocket costs for those with a high coinsurance that ranges from 20% to 33%, for example, could be pushed beyond affordability, particularly with the chronic nature of treatment (i.e., the emergent immunotherapies and the BRAF and MEK inhibitors).

By Gordon Gochenauer, Director, Oncology Commercial Strategies, Kantar Health

By Dave Johnson, Vice President, Encuity Research

At Encuity Research, we’ve been able to determine through our EventAnswers™ audit that pharmaceutical and biotech companies spent $3 billion on events in the past 12 months, with 12% of their budgets going to symposia like ASCO.  With the reality of today’s spend scrutiny, it is vital for manufacturers to understand how the information they present at events affects physician treatment decisions.  Showing up is no longer enough.  When it comes to event themes, there are perception winners and losers.

To get a sense of the impact that the 2013 annual meeting of ASCO had on physicians, we surveyed 100 oncologists who attended the event.  These oncologists highlighted new treatments for melanoma and cervical cancer as the most important subjects of new clinical information.  Specifically, new treatments for melanoma, with an emphasis on PD-1 treatments, were cited by 31% of respondents, while advances in the treatment of cervical cancer, particularly Genentech’s Avastin®, were cited by 20% of respondents (Figure 1).

Oncologists expressed that advances in immunotherapy was a key theme at the conference, in addition to news about glioblastoma multiforme and breast cancer treatments.  When asked what product-related information presented at this year’s ASCO conference they found most valuable, 41% of ASCO attendees highlighted news about Avastin.  Oncologists also cited information on PD-1 treatments (17%), nivolumab (11%), and Bayer/Onyx’s Nexavar® (10%) as the most valuable in 2013.

As in 2012, we found that oncologists overwhelmingly named Genentech as the company providing the most valuable information at ASCO in 2013.  Unaided, 84% of physicians named Genentech as providing the most valuable information, and Bristol-Myers Squibb moved to second with 43% of mentions, followed  by Novartis (29%), Merck (20%), and Celgene (16%).

ASCO attendees recognized Millennium and Seattle Genetics as up-and-coming players in the treatment of cancer; unaided, 13% of ASCO attendees cited Millennium as an up-and-coming company, followed closely by Seattle Genetics.  Sanofi, Pharmacyclics, Onyx, and Astellas rounded out the top companies.

Overall, 2013 ASCO attendees responding to our survey found the conference to be valuable.  Half of respondents rated it as very or extremely valuable, with 86% reporting that it was equal to or more valuable than the 2012 conference (Figure 2).

However, physicians reported that they were less likely to change patient treatment based on 2013 ASCO findings compared with the 2012 conference.  Just 16% of attendees indicated that they were very or extremely likely to change prescribing behavior following the 2013 conference, compared with 40% following the 2012 conference.

Products that had the strongest impact on physicians’ treatment plans included Avastin, Erbitux®, and tamoxifen.  We found that 22% of physicians surveyed will consider using more Avastin following the conference, 10% of physicians would use more Bristol-Myers Squibb’s Erbitux following conference, and 9% of physicians indicated plans to extend use of tamoxifen to 10 years (vs. the current standard of 5 years).

Using research such as this to measure and refine the impact of presenting at critical venues like ASCO is vital for a cost-conscious industry.  Through the use of turnkey research, companies can quickly illuminate the influence of their clinical information and promotional efforts on physicians’ perceptions, understanding, and intent to prescribe.

Download the ASCO Impact Report

Encuity Research—the market research and analytics subsidiary of Campbell Alliance—conducted this survey to evaluate the relevancy and effectiveness of company-sponsored clinical data and promotions.  The full results of the survey are summarized in the ASCO Impact Report, which provides an encompassing view of ASCO attendees’ intent to change treatment plans, their perceptions of clinical information presented, and their ratings of information offered by pharmaceutical and biotech companies.  For a full version the ASCO Impact Report, please visit http://www.encuity.com/asco.