European Society for Medical Oncology
This year’s European Society for Medical Oncology (ESMO) Congress was a great success, with record numbers attending over the five days. Attendees included over 13,000 oncologists and other healthcare professionals involved in cancer care, 360 media representatives and close to 400 cancer patients who participated in a dedicated seminar.
Dr Johann de Bono from the Institute for Cancer Research and Royal Marsden Hospital, Sutton, UK, presented results of the randomised double-blind placebo-controlled Phase III study that compared abiraterone acetate (potent and selective inhibitor of CYP17α-hydroxilyase) vs placebo in 1,195 patients with castration-resistant metastatic prostate cancer. This is the first clinical trial that prospectively studied hormonal therapy after docetaxel treatment and the first clinical trial in prostate cancer with prospective collection of circulating tumour cells. Overall survival data shows clear advantages in favour of abiraterone acetate compared to placebo (14.8 months vs 10.9 months) and the drug also significantly improved time to prostate-specific antigen (PSA) progression, radiographic progression-free survival, and PSA response rate. Fall in circulating tumour cells matches with the overall survival data and side effects show almost no difference in comparison to placebo.
OPTIMAL is the first prospective Phase III study demonstrating that erlotinib is superior to standard platinum-based chemotherapy in EGFR activating mutation-positive non-small cell lung cancer (NSCLC) patients. In studied Asiatic population progression-free survival was significantly prolonged with erlotinib in comparison to the standard chemotherapy (13.1 vs 4.6 months). The objective response rate was also significantly improved in the erlotinib arm (83% vs 36%). Survival data from the study is not available yet, and a confirmatory study in Caucasian is underway. The abstract was accompanied with a biomarker analysis which demonstrated that EGFR exon 19 mutation is the best predictor of efficacy and no additional biomarkers were identified to predict greater benefit of erlotinib vs gemcitabine/carboplatin in this patient population.
Dr Tim Perren from Leeds Teaching Hospitals NHS Trust, UK, reported findings from an international Phase III randomised trial, which included 1,528 women with high-risk early or advanced stage epithelial ovarian cancer, primary peritoneal cancer or Fallopian tube cancer. This is the second large positive randomised trial in ovarian cancer patients that met the primary endpoint of prolonging progression-free survival. Investigators demonstrated that at 12 months the risk of developing further progression of ovarian cancer was reduced by 15% when compared to the risk of progression seen with chemotherapy alone. The major benefit is obtained in sub-optimally de-bulked and advanced-stage patients. The results of ICON7 translational studies should identify the population who benefits from this treatment. The data concerning survival will not be mature for a further two years, but preliminary data shows an encouraging early trend with fewer deaths seen in patients treated with bevacizumab.
Treatment options for advanced neuroendocrine tumours are limited. In 429 patients with progressing well or moderately differentiated advanced neuroendocrine tumours and a history of carcinoid symptoms, everolimus – an oral inhibitor of mTOR pathway – was administered together with octreotide LAR and compared to placebo plus octreotide LAR. The study was presented by Dr Marianne Pavel of the Charité University Hospital, Berlin, Germany who showed a 5.1 month clinically meaningful increase in median progression-free survival for everolimus combination compared to placebo plus octreotide LAR. This should be considered for changing the current practice, as the alternative treatment is octreotide or a very aggressive chemoembolisation. Another clinically meaningful report on 410 patients with advanced low- or intermediate-grade pancreatic neuroendocrine tumours showed a 65% reduction in the risk of progression and an increase from 4.6 to 11.0 months in median progression-free survival when everolimus was combined with the best supportive care and compared to placebo plus best supportive care. This study was presented by Dr James Yao of the MD Anderson Cancer Center, Houston, USA.
Dr David Spigel, Sarah Cannon Research Institute in Nashville, USA reported results of a study that included 128 patients with advanced NSCLC. Patients were randomly assigned to treatment with either erlotinib plus placebo, or erlotinib plus novel agent MetMAb, a monoclonal antibody that binds specifically to the MET receptor. This is the second trial in lung cancer where targeting of MET receptor in combination with erlotinib suggests a better outcome. Immunohistochemically MET-positive population not only derived a benefit in progression-free survival, but also an almost statistically relevant overall survival benefit. A note of caution, however, is that these Phase II results should be validated in a Phase III trial.
Professor Leonard Bastian from Klinikum Leverkusen in Germany led a first international randomized trial testing a minimally invasive surgical technique, balloon kyphoplasty to non-surgical management in the treatment of cancer patients with vertebra compression fractures. The investigators found that this new technique offers effective relief in cancer patients with painful and debilitating spinal fractures and led to improved quality of life.
Dr Georgina Long from Melanoma Institute Australia and Westmead Hospital in Sydney, reported the results in a subgroup of 10 melanoma patients with previously untreated brain metastases from the international Phase I/II trial with the selective oral inhibitor of V600 mutant BRAF kinase. The investigators described activity of this targeted agent in brain metastasis and furthermore observed that the response in brain metastasis correlated with extra-cranial tumour response. These findings support further investigation of the agent in this difficult to treat patient population.
Although the LUX-lung 1 study did not meet its primary endpoint of extending overall survival, this does not diminish the potential value of afatinib (BIBW2992). The fact that this new irreversible inhibitor of EGFR/HER1 and HER2 induced objective regressions in heavily pre-treated NSCLC patients and led to a better progression-free survival with improvements in some of cancer-related symptoms, witnesses that the oncology community got a very active compound in the lung cancer field.
Most cancer patients suffer from chronic pain. Controlled studies with fentanyl pectin nasal spray demonstrate a rapid onset of effect and greater clinically meaningful pain relief compared to placebo and oral morphine. Potential advantages of nasal route are rapid absorption, no first pass metabolism, avoiding problem in mouth and swallowing. A new technology allows low volume, fine mist, and consistent particle size delivery and therefore controlled dosing. The study was presented by Dr Luis Torres of the Hospital Puerta del Mar, Cadiz, Spain who reported that fentanyl pectin nasal spray can be easily titrated to an effective dose and could be used across a broad range of opioid-tolerant cancer patients. This is an interesting study but still cannot lead to a change in the current practice. In addition, it’s a very good route of administration and has potential for many other drugs.
Trastuzumab has shown to improve disease-free and overall survival in patients with HER2-positive early-stage breast cancer. Standard adjuvant treatment with trastuzumab requires 52 weekly infusions over one year after chemotherapy and can result in discomfort, inconvenience and a significant time commitment for both healthcare providers and patients. Subcutaneous administration could significantly simplify treatment, shortening administration and improving patient experience. Recombinant human hyaluronidase (rHuPH20) has been developed and approved to improve dispersion and absorption of co-administered drugs. It has been combined with trastuzumab to allow injection volumes ≥3 mL to be safely and comfortably administered subcutaneously. Dr Chris Wynne of the Christchurch Clinical Studies Trust, Christchurch, New Zealand presented results of a phase Ib study in which subcutaneous trastuzumab showed even a tendency toward fewer administration-related reactions than i.v. trastuzumab; furthermore it achieved a serum exposure comparable to the approved i.v. formulation. The patient experience was favourable. The safety, tolerability and pharmacokinetic results of the study support the further testing of subcutaneous trastuzumab.
On the patient side, 400 representatives of patient advocacy groups discussed the long-term effects of cancer and the implications of rehabilitation for research and public policy at the 8th ESMO Patient Seminar. Today, 65% of cancer patients live more than five years after diagnosis. Nevertheless, being confronted with cancer and going through treatment is extremely traumatic and problems do not end with remission. Late effects include haematological, endocrine, cardiovascular, pulmonary, gastrointestinal, renal and sexual problems. Patients also report fatigue, pain, depression, loss of concentration and fear of relapse.
The word ‘cancer’ is used to refer to over a hundred different types of disease, as can be seen with the increasing use of molecular classification. This underlines the need for a multidisciplinary approach for every tumour type.
The ESMO President, Professor David Kerr, commented: “What has become clear is that we need to get back to our laboratories to understand more about the disease. We need more biology and a better insight so that we can treat the right patient, at the right time, with the right drug at the right dose. This ESMO Congress has been a great celebration of the bio-diversity of cancer leading to some, I believe, practice-changing clinical trials.”