The Annual Meeting of the American Society of Clinical Oncology (ASCO) descends upon us once again (June 1st through 5th in Chicago), and the newswires are alive with buzz and anticipation of the exciting, and often long anticipated, clinical data that will be presented at this major annual conference.
Indeed, all the talk in the Decision Resources oncology team is about ASCO the hotspots for each indication, healthy competition between analysts as to who is holding the most exciting indication and, of course, the more data presented the more work in the office for incorporating the news into our products and market forecasts.
There are numerous editorials and blogs regarding what are perceived to be the highlights. Here we describe just some of the data that are attracting our attention at Decision Resources.
Malignant Melanoma, historically largely devoid of exciting drug development, came of age last year with new drug approvals that have a real benefit to a proportion of patients, and at ASCO this year malignant melanoma will continue to excite as practice-changing data are revealed giving rise to the promise of new drug launches, perhaps as early as this year. The most anticipated data must be for the two targeted agents under development by GlaxoSmithKline: the BRAF inhibitor dabrafenib, and the MEK inhibitor trametinib. Data for both of these agents as monotherapies (from the BREAK series of studies and the METRIC study), will be showcased at ASCO and the observation that dabrafenib, perhaps unexpectedly, appears active against brain metastases which are frequent in cases of advanced melanoma is particularly noteworthy. However it is the combination of these two drugs that is currently most intriguing to us, and is the subject of much enthusiasm from key opinion leaders interviewed by Decision Resources. One of these thought leaders told us: The BRAF and MEK combination has a lot of things in its favor not only are we hopeful that the combination will provide a longer duration of response [than BRAF or MEK monotherapy], but also, looking at the data, it is clear that the side effects decrease with the combination. The combination decreases for sure the BRAF inhibitor side effects, and for reasons that we don't really understand it also decreases the MEK inhibitor skin rash and diarrhea.
The abstract for the BRAF/MEK inhibitor combination reports that administering the two drugs demonstrates an acceptable safety profile and most notably an apparently protective mechanism for trametinib against the development of basal cell cancers which are associated with the use of BRAF inhibitors. Cutaneous squamous cell skin carcinoma was reported in 2% of patients, in this small Phase I/II trial. In contrast, 24% of patients treated with the approved BRAF inhibitor, Roche's Zelboraf (vemurafenib) suffered the same toxicity.
We are currently updating our Event Driven Malignant Melanoma Pharmacor advisory service which will incorporate the new data presented at ASCO these data, along with primary research (surveys and interviews) will guide our updated, epidemiology-based, market forecast. Some of our challenges are how to position the second-to-market BRAF inhibitor, dabrafenib, in relation to the already widely used Zelboraf. Will trametinib secure approval as a monotherapy for melanoma. And will the potential for improved efficacy of the dabrafenib/trametinib combination in addition to the acceptable safety profile propel the dual-combination as the future treatment of choice for BRAF-mutated patients. And how will price and cost controls impact a potentially very high price combination treatment. Plus, the incorporation of other exciting developments such as in the vaccine and immunotherapy space.
Moving on to non-small cell lung cancer (NSCLC); one of the key highlights for this dire disease will be the new Phase III data relating to the irreversible EGFR inhibitor, Boehringer Ingelheim's afatanib (to be known as Tovok). Afatanib is in a series of clinical trials, termed LUX, for NSCLC, but the key afatanib data at this year's ASCO will be from the Phase III, LUX-3 trial comparing afatanib monotherapy to the widely used chemotherapy doublet pemetrexed (Lilly's hugely successful Alimta) and cisplatin in patients harboring the EGFR activating mutation. This setting for afatinib is comparable to the Iressa label in Europe, but distinct from Tarceva's U.S. label. Success for afatanib as a first-line treatment for this niche population could make it the agent of choice, leaving Tarceva as an option only for those patients without the mutation, or mutation status unknown. However, some experts believe that, as an irreversible inhibitor, afatanib may be better positioned after treatment with either Iressa or Tarceva and most are eager to see the performance of afatanib in head-to-head trials against established EGFR inhibitors (such trials are ongoing). Regardless, with the positive interim PFS data for Pfizer's dacomitinib also being presented at ASCO, it is highly likely that the EGFR TKI market is set to become increasingly complex and competitive in the near term and we model our views on this space in our NSCLC Pharmacor product; updates to incorporate the ASCO data will start soon.
The lack of a statistically significant OS benefit when Array/AstraZeneca's MEK inhibitor selumetinib is added to docetaxel for second-line treatment of locally advanced or metastatic NSCLC in 87 patients, who harbor a KRAS mutation, when Phase II data were announced last year, was clearly disappointing especially as the OS gain was in excess of four months. However, a statistically significant, 3.2 month gain in PFS is now reported and will be further elaborated at ASCO. In addition, an impressive response rate of 37% (versus 0% for docetaxel alone) is eye catching, but begs the question, what is the docetaxel adding to treatment in this setting. And could there be a better drug to combine with selumetinib. Regardless, both Array BioPharma and AstraZeneca will welcome the positive PFS and response data.
Much of the ASCO buzz for breast cancer surrounds the trastuzumab-conjugate TDM-1 notably the update of PFS data from the EMELIA study in the second-line setting which is investigating TDM-1 versus Tykerb plus Xeloda in patients that have progressed on Herceptin-based therapy. Roche released the news that PFS was significantly extended in the TDM-1 cohort and have filed for approval based on these data; oncologists are keen to discover the extent of the benefit. Decision Resources forecasts seven major market sales for TDM-1 of over $500 million in 2020. However, success in the ongoing MARIANNE study which is exploring the use of first-line TDM-1 would carry 2020 sales (seven major markets) close to $1 billion. Although a study of adjuvant TDM-1 is ongoing, our view is that pertuzumab has the potential of being a more compelling option for extended adjuvant treatment. You can find details of our HER2 positive breast cancer market in our Pharmacor product, along with our view on all the other breast cancer market segments, including the triple negative population a patient cohort with particularly high unmet need.
Another interesting antibody-based therapy to have data at ASCO is the first-in-class BiTE (bifuntional T-cell engager) agent recently acquired by Amgen from MicroMet. The modus operandi of this technology is for the BiTE molecule to bind antigens on two cell types, thereby engaging the two cells and facilitating cell death. In the case of blinatumomab, which is in most advanced for Acute Lymphoblastic Leukemia, the BiTE engages CD19 which is overexpressed on malignant B-cells, and CD3 on cytotoxic T-cells. Phase II data will be presented, and the abstract reveals that 26 of the 36 patients treated with blinatumomab across all of the tested doses and schedules achieved a complete response with partial hematologic recovery and all but two patients achieved a molecular response; data that are reported as superior to standard of care. Blinatumomab was well tolerated and no serious adverse events were observed. Indeed, blinatumomab has been highlighted by experts interviewed for our upcoming report (from Decision Resources Niche Markets and Rare Diseases portfolio) on ALL as one of the most promising agents with a potential role in both relapsed patients and for treating minimal residual disease as one expert told us: Blinatumomab could be quite revolutionary, but it's early days. But the chance of responding is very high. Its targeted therapy and it's really pretty clever the way it uses the patient's own immune system to eliminate leukemic cells.
Finally, a paper researching disparities in U.S. treatment rates for advanced cancer will also be presented. The findings show, perhaps unsurprisingly, a correlation with lack of treatment and race, age, lower income/lack of insurance. Of the nine cancers included in the study, more than half of those not treated with anti-cancer therapy (either drugs or radiotherapy) had lung cancer. However, the actual rates of non-treatment were, with the exception of prostate cancer, similar across tumor types; for example 25.4% of patients with renal cell carcinoma went untreated. Of course there are numerous factors at play; however the sometimes modest efficacy benefit versus high cost, and side effect profile will all contribute to whether physicians and patients opt for treatment. Indeed, the wider use of quality of life endpoints in clinical trials, and studies designed to look at older or poor performance status patients will help oncologist decision making in the future. One thing is certain, access to expensive cancer drugs is an increasingly important to factor in all markets. Decision Resources has a suite of products that explore market access and reimbursement issues and the increasingly significant influence of the payer, in markets across the globe.
So this completes our whistle-stop tour of just a few selected highlights from the many clinical trials that will be presented at ASCO. It looks like ASCO will be as exciting and stimulating as ever and it is, of course, reassuring to see that some gains are being made in patient outcomes for a number of malignancies.