This is the third time that Vienna has played host to the ESMO Congress, with previous congresses taking place in 1996 and 2004. It’s interesting to look back at which topics were ‘hot’ in previous years as it provides great testimony to the vast amount of progress made in oncology as a result of the collective translational and clinical research we have undertaken over the past 20 years.
In 1996, data reported at the ESMO Congress included further attempts to fully characterise the genetic aberrations associated with BRCA1 breast cancer following the first identification of this breast cancer-associated gene in 1990. These included a presentation by Dr F Goldwasser from the Hopital Paul Brousse, Vlllejuif, France, on the first documented polymorphism of the anti-proliferative protein encoding gene, prohibin (PHB) (abstract 70); as well as various reports to further evaluate the prevalence of BRCA1 gene alterations in breast cancer populations (abstracts 16P, 23P and 24P). However, by 2004, much more was known about BCRA1 and BCRA2 in breast cancer, and at this year’s congress, ESMO are very proud to be launching the 4th version of the ESMO Clinical Practice Guidelines of BRCA in breast cancer, which includes screening and prevention strategies as well as treatment recommendations derived from evidence-based medicine.
It is also interesting to note that many of the targeted agents used in everyday clinical practice today were still in early preclinical development in 1996. However, by 2004, many of these were emerging as efficacious agents, supported by robust data from Phase 3 clinical trials. For example, findings from the BR.21 study showed that treatment with the epidermal growth factor receptor (EGRF) inhibitor, erlotinib, was associated with a survival benefit as in patients with advanced non-small-cell lung cancer (NSCLC) when used as > 2nd line therapy; and findings from the BOND study showed that the addition of the EGFR inhibitor, cetuximab, to irinotecan improved both response rate and disease stabilisation in patients with EGFR-expressing, chemorefractory colorectal cancer. In recent years, research efforts have focussed on refining the use of these agents, with a view to moving towards a tailored approach to therapy. Indeed, this is reflected in the ESMO 2012 Congress programme, which includes various presentations reporting the efficacy of targeted agents such as erlotinib and cetuximab in specific patient populations. In addition, the efficacy and safety of various new drugs with novel molecular targets will also be presented.
By 1996, trastuzumab had already entered clinical development and by 1998, it had been approved for the treatment of HER2 positive metastatic breast cancer (MBC). Research presented at ESMO 2004 showed that radiolabeled trastuzumab could identify HER2-positive lesions and might possibly assist in detecting metastases and predicting treatment response. At this year’s meeting, survival data from EMILIA, a Phase 3 study of trastuzumab emtansine (T-DM1) versus a combination of capecitabine and lapatinib in HER2-positive locally advanced or metastatic breast cancer will be presented. T-DM1 is an antibody-drug conjugate incorporating the HER2-targeted antitumor properties of trastuzumab with the cytotoxic activity of the microtubule inhibitor, DM1, conjugated by a stable linker. Data from CEREBEL (EGF111438), an open-label randomised Phase 3 study comparing the incidence of CNS metastases in patients with HER2-positive MBC, treated with lapatinib plus capecitabine versus trastuzumab plus capecitabine will also be presented. Debate about the optimal duration of treatment with trastuzumab in patients with HER2 positive early breast cancer has been ongoing since the first results in 2005. Data from the Herceptin Adjuvant (HERA) trial and Protocol for Herceptin® as Adjuvant therapy with Reduced Exposure (PHARE) trial comparing 2 versus 1 year and 12 versus 6 months of trastuzumab, respectively, after adjuvant chemotherapy will hopefully clarify the optimal duration of trastuzumab in this patient population.
Finally, data from earlier ESMO meetings have shown that chemotherapy could be given to melanoma patients but with limited success. However, since then, therapeutic targets have been identified in melanoma, and today biological agents lead the way in the management of this aggressive type of cancer. Indeed, earlier this year, the BRAF inhibitor, vemurafenib, was approved as monotherapy for the treatment of adult patients with BRAF V600 mutation positive unresectable or metastatic melanoma. During this year’s ESMO Congress, we will learn more about the activity of next-generation targeted agents such as the combination of BRAF/MEK inhibitors in patients with BRAF-V600E mutated melanoma.