Decision Resources. Pharmaview team will be present at the annual American Society of Clinical Oncology (ASCO) conference in Chicago, from the 31st of May through the 4th of June 2013. We shall provide our insights and analysis on the major breakthrough therapies, updates in treatment algorithms, and novel pathways of interest in the treatment of cancer. Below is a summary of key abstracts and data which we expect will be highlights at this year's conference.
We Cannot Get Enough of Avastin
Avastin will be a heavily featured drug at this year's meeting with two presentations at the June 2nd plenary session assessing the drug's potential in newly diagnosed glioblastoma (Abstract #1) and recurrent ovarian cancer (Abstract #3).
Avastin in newly diagnosed glioblastoma
Avastin was granted accelerated FDA approval for refractory glioblastoma multiforme in 2009. The Phase III AVAglio trial investigating Avastin in combination with temozolomide and radiotherapy met its co-primary endpoint of PFS in August 2012 but full results released in November 2012 showed the other co-primary endpoint of overall-survival (OS) was not met. Eagerly anticipated results from the RTOG 0825 trial, which has a similar clinical design to AVAglio will be presented at the June 2nd plenary session. There is a very high unmet need in newly diagnosed glioblastoma and temozolomide is the current benchmark therapy but experts interviewed by Decision Resources report that Avastin is already used off-label in newly diagnosed glioblastoma. We expect the PFS improvement shown in AVAglio to be sufficient to warrant use of Avastin as an effective option in this patient population. Should results from RTOG 0825 show an OS benefit, this will place the drug in an even more favorable position.
Avastin VS Erbitux in first-line colorectal cancer (#Abstract 3505)
In the US, Avastin is the gold standard in first-line KRAS wild-type colorectal cancer, even though Erbitux in combination with FOLFIRI received a line expansion for this patient population in the US in July 2012. In Europe, where Erbitux has been approved in this setting since 2008, the situation is less clear cut. Results from FIRE-3, a head-to-head study led by the University of Munich and sponsored by Merck (European marketer of Erbitux) is looking at FOLFIRI plus Avastin versus FOLFIRI plus Erbitux in first-line KRAS wild-type colorectal cancer. We expect the impact of results from FIRE-3 to be minimal in the US, where physicians tend to use FOLFOX in combination with Avastin rather than FOLFIRI, and restrict Erbitux and other agents with a biomarker for the later lines where the patients suffer from more advanced disease. In the EU, where Avastin is more often administered in combination with FOLFIRI, strong results in favor of Erbitux could lead to an increase in its first-line sales, particularly if the safety profile is good. Strong data could also help Merck to promote its drug over key rival Vectibix.
Another Interesting Year For Anti PD-1 Candidates
Last year's conference featured PD-1 antibodies, with BMS' nivolumab leading the way. Phase I data of nivolumab in solid tumors have indicated a better toxicity profile than BMS's other immunotherapy Yervoy, which is experiencing strong uptake in melanoma. Nivolumab, unlike Yervoy, will also have the advantage of a potential biomarker a feature which could set anti PD-1 drugs apart from other immunotherapies. This year's ASCO should shed light on which drugs in this emerging class are best positioned. Some interesting PD-1/PD-L1 related data expected at ASCO 2013 include;
- Nivolumab in combination with Yervoy in patients with metastatic melanoma (Abstract # 9012). Preliminary data has shown that that this combination achieved an objective response rate of 40%. It is believed combining nivolumab with Yervoy could enhance the latter's efficacy and possibly reduce some of its toxicity. Use in combination would also help BMS minimize cannibalization of Yervoy by the newer drug.
- Results of a Phase I/II trial looking at nivolumab with a peptide vaccine in patients who are naïve to or resistant to Yervoy (Abstract # 9011) will also be reported at ASCO this year.
- Lambrolizumab (MK-3475) is being investigated by Merck & Co in patients with advanced melanoma. Interim data from an early phase trial presented at the International Congress of the Society of Melanoma Research showed that 51% of patients received an objective response. (Abstract #9009). Lambrolizumab was also awarded FDA breakthrough therapy in April 2013, which could accelerate its development and reduce nivolumab's head start.
- MPDL3208A (RG7446), Roche's anti PD-L1 agent, will also report results from an early Phase trial looking at efficacy, safety and biomarkers in locally advanced or metastatic melanoma (Abstract # 9010). At present, the drug is furthest behind in development so any points of differentiation will be key. We believe it is likely that Roche will also apply for breakthrough status, if it has not already done so. The company's strong diagnostics division and personalized medicine approach could be an advantage in the race to develop an anti-PD-1 drug.
Table 1 below features other interesting data which we await at this year's conference.