How the 35th ESMO Congress presentations challenge criteria for changes in oncology practice
In this ESMO Scientific E-News we cover some of the studies presented during the 35th ESMO Congress in Milan and analyse their implications to the oncology practice. The ESMO scientific meeting report with detailed analysis will be delivered in one month. The full impact of presented studies will be available upon their publication in peer-reviewed journals and ESMO will be delighted if abstract presenters consider our flagship journal, Annals of Oncology (new IF 5,647) to submit their manuscripts. The ESMO is also delighted because some of the study results presented during the Congress will be submitted to the regulatory agencies for approval in coming months.
Studies presented at ESMO 2010
Abiraterone acetate demonstrates breakthrough results in the management of castration-resistant prostate cancer
Dr Johan de Bono of 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, designed originally in an academic institution) vs placebo in 1195 patients with castration resistant metastatic prostate cancer. This is the first trial that prospectively studied hormonal therapy after docetaxel treatment and the first clinical trial in prostate cancer with prospective collection of circulated tumour cells (CTC). In addition, it is the first trial that prospectively used Prostate Cancer Clinical Trials Working Group Criteria in the context of randomised phase III trial. Overall survival data shows clear advantage in favour of abiraterone acetate compared to placebo (14,8 months vs 10,9 months) and the drug also significantly improved time to PSA progression, radiographic progression-free survival, and PSA response rate. Fall in CTC matches with the overall survival data and side effects show almost no difference in comparison to placebo. Further follow-up on survival data is awaited as well as report on long-term side effects.
Erlotinib improves progression-free survival in EGFR activating mutation-positive NSCLC patients
The OPTIMAL is the first prospective phase III study demonstrating that erlotinib is superior to standard platinum-based chemotherapy in EGFR activating mutation-positive 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 with erlotinib (83% vs 36%). Survival data from the study are not available yet, and a confirmatory study in Caucasian is underway. The abstract was accompanied with the biomarkers analysis on KRAS, EGFR T790M, HER2, BRAF, PIK3CA, PTEN mutations and c-MET amplification status. The biomarkers study 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 population of patients.
Everolimus shows an important progress in the treatment of patients with advanced neuroendocrine tumours
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. In this large phase III randomised controlled trial for this rare type of cancers, everolimus combination provided a 5.1 month clinically meaningful increase in median progression-free survival 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 of more than 6 months in median progression-free survival from 4.6 to 11.0 months when everolimus was combined with the best supportive care and compared to placebo plus best supportive care.
ICON 7 improves progression-free survival in ovarian cancer patients by adding bevacizumab to standard chemotherapy
Dr Tim Perren from Leeds Teaching Hospitals NHS Trust, UK, reported findings from the international phase III randomised trial, which included 1528 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 and it met the primary endpoint. 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 ICON 7 translational studies should identify the population who benefits from this treatment. The data concerning survival will not be mature for a further 2 years, but preliminary data show an encouraging early trend with fewer deaths seen in patients treated with bevacizumab. Being an option with the currently best achieved treatment outcomes, bevacizumab arm should be taken as a standard comparator in further clinical research.
The 35th ESMO Congress should be also remembered by presentations on novel targeted agents and randomised surgical trials for which a further validation of results is needed
- Dr David Spigel, Director of lung cancer research for the Sarah Cannon Research Institute in Nashville, Tennessee reported results of study that included 128 patients with advanced NSCLC. Patients were randomly assigned to treatment with either erlotinib plus placebo, or erlotinib plus MetMAb, a monoclonal antibody that binds specifically to the MET receptor. This is the second trial in lung cancer where targeting of MET 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 statistical overall survival benefit, which is remarkable taking into account the small number of patients. One 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 randomised 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 GSK2118436 in this difficult to treat patient population.
- Dr Edith Perez of the Mayo Clinic in Florida presented the results of the first ever randomised trial of trastuzumab-DM1 (T-DM1) as a first-line treatment for HER-2 positive metastatic breast cancer. In the trial, researchers randomly assigned 137 patients to treatment with either trastuzumab plus docetaxel, or T-DM1. After a median of approximately 6 months of follow-up, they found a similar overall response rate but the rates of clinically relevant adverse events were lower in the T-DM1 arm. The second important implication of this study is that it proves the concept that linking a monoclonal antibody to a cytotoxic drug leads to an anticancer effect.
- Although the LUX-lung 1 study did not meet its primary endpoint of extending 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 pretreated NSCLC patients, and led to a better progression-free survival with improvements in some of cancer-related symptoms, witness that the oncology community got a very active compound in lung cancer field.