The OBR Blog

June 27, 2014 - 12:06 pm Posted in Featured comments0 Comments

Introduction

In an effort to provide you with timely market feedback from ASCO 2014, OBR and MDoutlook are pleased to share results from MDoutlook’s OncoPolls™ from the meeting. This first report explored presentations in colorectal cancers (CRC).

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 2014. Launched two days after close of 2014 American Society of Clinical Oncology (ASCO) Annual Meeting, held in Chicago, IL., May 30-June 3, 2014
  • 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: 50 on June 24th
  • No financial incentives provided for participation

Geographic Distribution of Respondents

Attendance at 2014 ASCO Annual Meeting

Key Conclusions

  • Nearly three quarters of survey respondents attended this year’s ASCO annual meeting
  • Higher proportion of attendees than in previous years (typically has been a 50/50 split)

Survey Participants’ GI Cancer Patient Flow:  Average Over 13 Cases Each Month

Key Conclusions

  • Survey participants* averaged 35 cases of colorectal cancer last 3 months
    • More than all other gastrointestinal cancers combined
  • Cases of pancreatic cancer were much more common than HCC

* Survey Participants = Medical Oncologists with an identified clinical interest in gastrointestinal cancers

Inclusion of Bevacizumab or Cetuximab with 1st Line Chemotherapy for KRASWT mCRC: Impact of the CALGB/SWOG 80405 Trial

Key Conclusions

  • Results of the CALGB/SWOG 80405 Trial are not going to change treatment usage in the 1st line setting
    • Small increases in cetuximab usage are expected, but not at the expense of bevacizumab
  • Inclusion of biologics with chemotherapy for 1st line setting is going to remain the standard of care
    • FOLFOX is and will remain the standard chemotherapy backbone for mCRC

Adjuvant Chemotherapy for Localized Rectal Cancer: Impact of the ADORE Trial Results

Key Conclusions

  • Oncologists recognize the clinical importance of the ADORE trial
    • Over half rate the presentation as important or higher
  • Due to these results, usage of adjuvant therapy for stage II rectal cancer is expected to increase by over 1/3 from current levels
    • Usage will be nearly 60% of the amount for stage III disease
  • Widespread usage of adjuvant therapy for stage III disease will continue
    • Slight increase to 80% of cases

Conclusions: Impact of ASCO 2014 on Clinical Practices for Colorectal Cancers

  • Colorectal cancer is the main type of gastrointestinal cancers seen in clinical practices
    • Oncologists’ patient flow in colorectal cancer is ~85% of their GI cancer patient flow
  • FOLFOX + bevacizumab is and will remain the most common 1st line treatment approach for KRASWT metastatic colorectal cancer
    • Minor increases in usage of cetuximab are expected, but not at the expense of bevacizumab
    • Chemotherapy with a biologic is the standard of care in the 1st line setting
    • FOLFOX will continue to be preferred over FOLFIRI
  • Adjuvant chemotherapy is seen as an important therapeutic approach for stage II and III rectal cancers
    • A 35% increase in its usage for stage II disease is expected, so that nearly half of patients will receive it
    • Widespread usage for stage III disease will expand even more, to 80% of patients
  • Oncologists use a wide variety of sources to learn about the results presented at ASCO

For a more detailed analysis report, please click here to download the full report.

Submitted by Robert Stephan, Sr. Director Medical Services and Strategy; Jessica Harnisch, Assoc. Global Medical Analyst; Justin Boag, Consultant; and Jan Heybroek, President MDoutlook.

June 23, 2014 - 09:06 am Posted in Featured comments0 Comments

By Dave Johnson, Vice President, Encuity Research

The sentiments of oncologists following their experiences at ASCO translate into prescribing behaviors throughout the year. At Encuity Research, we know that the perceptions oncologists take away from ASCO are of high interest to pharmaceutical and biotech companies developing and commercializing products in this space.

To get a sense of the impact that the 2014 annual meeting of ASCO had on physicians, we surveyed 100 oncologists who attended the event. Oncologists reported that themes centered on new treatments for prostate cancer were the most important new clinical information presented at this year’s ASCO conference. Treatments for breast cancer, melanoma, lung cancer, and chronic lymphocytic leukemia (CLL) followed. Specifically, new treatments for prostate cancer, with an emphasis on docetaxel, were cited by 35% of respondents, while advances in the treatment of breast cancer were cited by 18% of respondents (Figure 1).

Physicians rated information on Janssen/Pharmacyclic’s Imbruvica in chronic/small lymphocytic leukemia and mantle cell lymphoma the highest for overall value of information at the conference. Top-rated product themes also included Bristol-Myers Squibb’s nivolumab and Yervoy. Information related to Imbruvica in chronic/small lymphocytic leukemia and mantle cell lymphoma was highly rated by 73% of physicians, while information related to nivolumab and Yervoy in melanoma were highly rated by 59% of physicians.

Unaided, ASCO attendees highlighted news about Imbruvica and Sanofi’s Taxotere as the most valuable product information presented at the 2014 ASCO conference. Both products were cited by 20% of respondents. Nivolumab (18%) was close behind, while Yervoy (10%), Eli Lilly’s ramucirumab (9%), and Astellas/Medivation’s Xtandi (9%) rounded out the top products.

As in 2012 and 2013, oncologists overwhelmingly named Genentech/Roche as the company providing the most valuable information at ASCO in 2014. Unaided, 66% of physicians named Genentech/Roche as providing the most valuable information, with Bristol-Myers Squibb in second with 35% of mentions, followed by Novartis (26%), Pfizer (22%), and Merck (20%).

ASCO attendees recognized Pharmacyclics (11%), Gilead (10%), and Teva (9%) as the top three up-and-coming companies in the treatment of cancer. Seattle Genetics ranked fourth (7%).

Oncologists who attended the 2014 ASCO meeting gave the conference high overall ratings for its value. Over half of physicians rated it as very or extremely valuable, with 94% reporting that it was equal to or more valuable than the 2013 conference. (Figure 2).

Not only did oncologists find the conference valuable, it was also influential. The percentage of physicians who reported that they are more likely to change patient treatment based on 2014 ASCO findings increased compared with the 2013 conference. Nearly one-quarter (24%) of attendees indicated that they were very or extremely likely to change behavior following the 2014 conference, versus just 16% following the 2013 conference.

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.

June 16, 2014 - 10:06 am Posted in Featured comments0 Comments

Over the course of five days during ASCO 2014, data from hundreds of clinical trials were shared, answering the question of whether there’s a new treatment option for cancer patients. Increasingly, despite approval the FDA doesn’t have the final say on whether the drug in question represents a viable treatment option for potential patients. Payers too are exerting influence over treatment options through prior authorization requirements, as well as patient cost sharing, which can threaten affordability. In an era when the cost of a course of therapy with branded cancer drugs is typically measured in the tens of thousands of dollars and, not infrequently, over $100,000, FDA approval is no longer sufficient for treatment selection. Accessibility and affordability have become essential considerations as well.

CALGB 80405: Fodder for prior authorization and pathways?

The results of this large, Phase III trial were widely anticipated to elucidate conflicting data presented at ASCO in 2013, which demonstrated a survival benefit of Erbitux over Avastin in the first-line treatment of KRAS wild-type colorectal cancer (CRC)1 in the absence of a progression-free survival (PFS) benefit.

Treatment pathways are becoming a more prevalent means of managing cancer treatment, and CRC is one of the three most common cancers to be the subject of pathways. Whether initiated by payers or practices, treatment pathways are designed to drive selection of “preferred” treatment modalities and products. These products generally represent the most cost-efficient, evidence-based means of treating patients at each line of therapy. While demonstrated efficacy is usually paramount, tolerability and cost are also given critical consideration. When clinical outcomes are comparable, cost is usually the most important driver.

The secondary but important factors of cost and administrative burden already favor Avastin over Erbitux, and prescribing patterns clearly show a preference for Avastin over Erbitux in first-line, even in patients with the KRAS mutation. The lack of difference in efficacy between Avastin and Erbitux revealed in CALGB 80405 presumably removes the clinical efficacy rational for selecting Erbitux in the first-line setting. Payers may further leverage prior authorization to not only require biomarker testing for KRAS but also the use of Avastin before the more costly Erbitux will be covered. Such action may prompt practices to avoid the administrative burdens associated with Erbitux use. Pathways will likely be leveraged by both payers and oncology practices to further solidify the dominance of Avastin in first-line CRC.

EORTC 18071: How much of a good thing is too much?

Malignant melanoma is infamous its poor prognosis. When Yervoy launched in 2011, it represented not only improvement in median overall survival but also the chance at long-term survival for some patients. However, this clinical benefit came with an unprecedented (at the time) price among cancer treatments of $100,000 to $120,000 for a four-cycle course of treatment.

The strong positive recurrence-free survival data reported in EORTC 18071 for Stage III melanoma patients receiving adjuvant treatment with Yervoy represents a significant advance. However, the cost per cycle in the adjuvant setting is more than three times greater than for the current indication of metastatic disease, due to higher dosing. Further, treatment continues after the initial four rounds with maintenance infusions every three months for up to three years. At the current WAC price of Yervoy, a first year of adjuvant treatment will likely exceed $300,000, a cost likely to spark renewed scrutiny among payers. Until Yervoy receives an FDA indication or National Comprehensive Cancer Network (NCCN) guideline recommendations (level IIb or higher), oncology practices are likely to experience claims rejections due to a dose in excess of the indication.

Closing Thoughts

We are in an exciting era of clinical development of cancer treatment. Oncologists and hematologists have an unprecedented array of tools at their disposal to extend the lives of cancer patients. Biopharmaceutical companies have invested countless years and billions of dollars to bring these drugs to market. This investment and the unmet needs that these drugs address are reflected in high prices that are driving explosive growth in spending on cancer care. Not only do physicians have more “tools in their toolbox,” but payers have a growing armamentarium of tools that at their disposal to help rein in the cost trend. Be it through pathways, prior authorization, formulary tiers or cost sharing, payers will continue to leverage these tools to exercise influence over drug selection and utilization. Clinical evidence is and will remain the single most important determinant of access in the U.S., but the evidence can no longer be viewed in scientific isolation. Not only payers but also patients and physicians will weigh the evidence within a broader value context that takes price, therapeutic alternatives and outcomes into account.

1Heinemann, Abstract LBA3506, ASCO 2013.

By Debbie Warner, Vice President, Commercial Planning, Kantar Health

June 03, 2014 - 02:06 pm Posted in ASCO Conference Coverage comments0 Comments

Both Imbruvica® (ibrutinib, Pharmacyclics/Johnson & Johnson) and idelalisib (Gilead) are generating a lot of excitement as potential treatment options in non-Hodgkin’s lymphoma (NHL) and chronic lymphocytic leukemia (CLL).  Arzerra® (ofatumumab, Genmab/GSK) is currently approved for use in refractory CLL patients in both the United States and Europe. Although Arzerra is the second most utilized agent in the United States in CLL patients after their second relapse, it is still only used in 14% of U.S. CLL patients.1 This utilization rate highlights the unmet need for more therapies and helps partly explain the level of excitement for new therapies such as Imbruvica and idelalisib.

Imbruvica, an inhibitor of the Bruton’s tyrosine kinase (BTK), has already garnered accelerated approvals as a monotherapy for both mantle cell lymphoma and CLL based on Phase II data. While evaluation of these two applications were ongoing with the FDA, Pharmacyclics initiated a Phase III trial (RESONATE™) that compared Imbruvica versus Arzerra in 391 patients with multiple relapsed/refractory CLL or small lymphocytic lymphoma, with a median of two or three prior therapies, depending upon the treatment arm. In January 2014, the companies announced that the trial met its primary endpoint of progression-free survival (PFS) as well as the secondary OS endpoint.  Interim results of the trial were presented in one of the last oral presentations of the American Society of Clinical Oncology (ASCO) 2014 conference.2

The presenter, Dr. Byrd, stated upon presentation of the primary endpoint data (independent review committee-assessed PFS) that “a picture is worth a thousand words,” and the data in this case supported his statement. Imbruvica was far superior to Arzerra, as it was associated with a 78.5% reduction in the risk of disease progression. The median PFS was not reached in the Imbruvica arm and was 8.1 months in the Arzerra arm (HR 0.215, p<0.0001). It also was associated with a 56.6% reduction in the risk of death, with the median overall survival (mOS) not reached in either arm (HR 0.434, p=0.0049). This hazard ratio could have been even more in Imbruvica’s favor, but 29.1% of the patients treated with Arzerra were treated with Imbruvica at crossover after progressive disease. The overall response rate (ORR) was also significantly improved in the Imbruvica arm (42.6% versus 4.1%, p<0.0001). Importantly, Imbruvica’s PFS benefit was also seen in the subsets of patients with del17p (HR 0.25) or purine analog refractory disease (HR 0.18).

Imbruvica was generally well tolerated, but physicians will need to keep note of its associated toxicities.  Imbruvica was associated with increases in diarrhea (all grades, 47.7% versus 17.8%) and nausea (26.2% versus 18.3%). However, these few instances of increased toxicities were not associated with an increased drug discontinuation rate (4.1% versus 3.6%). Several toxicities had been of concern with Imbruvica but may be less so given this data. The rate of Grade 3 or higher infections was similar between the two arms (24% versus 22%), but these values must be considered in the context of a much longer time of treatment for patients on Imbruvica. The incidence of any grade of atrial fibrillation was higher among patients on Imbruvica (5% versus 0.5%); however, this caused discontinuation in only one patient.  Bleeding-related adverse events of any grade were more common with Imbruvica (44% versus 12%), but most were Grade 1.

However, other data presented at the conference might be of equal interest to clinicians. Dr. O’Brien presented a long-term analysis of the Phase I PCYC-1102 trial of Imbruvica monotherapy in a mixed patient population – both newly diagnosed and relapsed or refractory – with CLL.3,4,5 After three years post-initiation of Imbruvica, 64% of patients remain on the drug (81% of newly diagnosed, 58% of relapsed/refractory). Most of the adverse events were detected in the early stage of treatment and diminish with time. Also, as treatment continued, patients with responses less than a partial response (PR plus lymphocytosis) converted to a true PR, resulting in an updated response rate of 85%.

As noted above, these data are presented in a disease that has very strong competition. In particular, these data come after release of Phase III data for the PI3Kδ inhibitor idelalisib, in which the efficacy of idelalisib to Rituxan® (MabThera® in Europe, rituximab, Biogen Idec/Roche) was evaluated in 220 relapsed or refractory CLL patients. As presented at the 2013 American Society of Hematology (ASH) conference, idelalisib significantly improved PFS (HR 0.15, p<0.0001) and OS (HR 0.28, p-0.018).6 These data are expected to support FDA approval shortly, which will put Imbruvica and idelalisib in direct competition in the relapsed/refractory CLL setting. In the absence of a head-to-head trial, it might be hard for physicians to choose between these two highly effective and very tolerable agents. In this case, first-to-market may play a role, and this factor favors Imbruvica, which has been approved since February 2014. Other new targeted therapies, such as Gilead’s SYK inhibitor GS-9973 or AbbVie’s Bcl-2 inhibitor ABT-199, are further behind in development.

Although as the discussant (Dr. Lamanna) noted that there might be instances where cytotoxic chemotherapy will still be preferable in relapsed CLL patients, we have entered a new era of targeted therapy in CLL. Doctors will need to choose between many effective therapies, but in the view of patients this will be a good problem. As all of these agents have already or will soon initiate further Phase III trials in earlier lines of CLL, future competition between these agents is expected to be fierce.  We look forward to seeing more cases where a “picture is worth a thousand words.”

By Arnold DuBell, Ph.D., Consultant, and Stephanie Hawthorne, Ph.D., Senior Director, Kantar Health

__________________________________________________________________________________

[1] Kantar Health, CancerMPact® Treatment Architecture United States, accessed June 3, 2014.

[2] Byrd, Abstract LBA7008, ASCO 2014

[3] O’Brien, Lancet Oncology, 2013

[4] Byrd, NEJM, 2013

[5] O’Brien, Abstract 7014, ASCO 2014

[6] Furman, Abstract LBA6, ASH 2013

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