The annual European Society for Medical Oncology (ESMO) 2018 Congress took place from 19-23 October 2018 in breathtaking Munich, Germany. Held under the tagline “Securing access to optimal cancer care”, the conference offers a multi-professional platform for education and exchange to researchers, clinicians, cancer nurses, industry partners and patient advocates from over 130 different countries. The ESMO conference is one of the most important scientific conferences in the field of clinical cancer research.
“-ib” remains hip
Several presentations during this year’s meeting highlighted that the era of targeted therapies is not completely over yet. Most notably, the striking results of alpelisib (alpha selective PI3K inhibitor) in post-menopausal women with advanced breast cancer carrying a PI3KCA mutation. The SOLAR-1 phase III clinical trial demonstrated not only a substantial and significant progression free survival (PFS) benefit but also importantly a manageable tolerability profile in patients treated with the combination of alpelisib and fulvestrant (Abstract LBA3-PR). After a median follow-up of 20 months, median PFS was 11.0 months versus 5.7 months, for the combination versus placebo arm, respectively, with a hazard ratio (HR) of 0.65 [95% confidence interval (CI) 0.50 to 1.25, p=0.00065].
The ALESIA phase III clinical trial confirmed the superiority of the ALK inhibitor alectinib over crizotinib in first line, ALK positive non-small cell lung cancer (NSCLC), specifically in Asian patients. Most notable was the significant activity against CNS metastasis (abstract LBA10). The trial reported a significant improvement in PFS with alectinib, with a median PFS not yet reached compared with 11.1 months with crizotinib (HR, 0.22; 95% CI, 0.13-0.38; P<0.0001). An analysis that included patients with CNS lesions (measureable or unmeasurable) showed response rates of 72.7% and 21.7% with alectinib and crizotinib, respectively. The median duration of CNS response was 3.7 months with crizotinib and not yet reached for alectinib.
PARP continues showing positive data
In the field of PARP inhibition, such inhibitors continue to generate positive data. More specifically, data from the SOLO-1 clinical trials support the use of olaparib even earlier as maintenance therapy in ovarian cancer. The current approval of olaparib in ovarian cancer is for patients carrying BRCA mutations and having had a minimum of three prior lines of chemotherapy. To be eligible for SOLO-1, patients must have had newly diagnosed, advanced (FIGO stage III–IV), BRCA-mutated disease and responded to one prior (first-line) platinum therapy. With a median follow-up of 41 months, the investigator-assessed PFS in the olaparib arm was not reached, compared to 13.8 months in the placebo arm (HR 0.30; 95% CI, 0.23-0.41, p <0.0001). Furthermore, patients who received olaparib maintenance showed a statically significant improvement in PFS2, with a median PFS2 not reached, compared with 41.9 months in the placebo group (HR, 0.50; 95% CI, 0.35-0.72; P =0.0002).
The STAMPEDE trial continues to support treatment-changing practices in prostate cancer. Over the last few years and based on the CHAARTED, LATITUDE and STAMPEDE-abiraterone trial data, androgen depravation therapy (ADT) together with either docetaxel or abiraterone acetate have emerged as the standard of care in metastatic hormone naïve prostate cancer (mHNPC). One of the last reporting arms of the STAMPEDE clinical trial was set up to investigate whether treatment directed at the primary tumour would provide benefit to men with mHNPC. Retrospective data analysis demonstrated that addition of localized radiotherapy (prostate only and not to the whole pelvis) to the standard of care improved failure free survival (FFS) irrespective of the extent of metastasis. Overall survival (OS) also improved but only for patients with oligometastatic (low volume) disease (abstract LBA5_PR). In patients with low volume disease, a 3-year OS benefit of 8% in favour of the radiotherapy group was seen (HR 0.68, 95% CI 0.52-0.90, p = 0.007).
Immunotherapy keeps on being a winner
News on immunotherapy is hardly news anymore but no less noteworthy and important for clinicians and their patients. Promising activity signals continue to be reported in advanced disease, in combination with other agents including chemotherapy or other therapies targeting, as for example molecules that target angiogenensis and DNA damage response pathways. Clinical improvement is also being reported in earlier disease settings, such as stage III lung cancer and non-muscle invasive bladder cancer. Most noteworthy results were reported in first line metastatic triple negative breast cancer (mTNBC). In the IMpassion130 clinical trial, the combination of atezolizumab plus nab-paclitaxel was tested against placebo plus nab-paclitaxel (abstract LBA1_PR). Patients who were PD-L1 positive (≥1%) and who received atezolizumab plus nab-paclitaxel combination experienced significantly improved PFS and OS compared to those who received atezolizumab plus placebo (PFS of 7.5 months versus 5.0 months, HR, 0.62; 95% CI, 0.49 to 0.78; P<0.001 and OS of 25.0 months versus 15.5 months, HR 0.62; 95% CI, 0.45 to 0.86).
Importance of early detection through ctDNA
The importance of early disease detection and how this may be achieved through assessment of circulating free (cf), tumour (t) DNA or circulating tumour cells (CTCs), formed the basis for various symposia and presentations. The work of Dennis Lo (Chinese University of Hong Kong) in nasopharyngeal cancer is exemplary in this regards. During a 3-year period they have collected over 20,000 blood samples and screened them for Epstein–Barr Viral (EBV) DNA, a virus that is highly prevalent in South-East Asia and closely linked to the development of nasopharyngeal cancer. The EBV cDNA screening assay they have developed has 97.1% sensitivity and 99.3% specificity, false positive rate of 0.7% and positive predictive value of 19.5%. This is based on testing a single blood sample collected at one time point. Furthermore, the group are working on understanding in more detail how certain characteristics such as circulating DNA size and concentration may be able to be extrapolated to tumor (rather than viral) DNA.
Quality of Life updates in study designs
Interesting developments related to the design of clinical trials were also discussed during the meeting. The European Organisation for Research and Treatment of Cancer (EORTC) presented EORTC QLQ-BR45, the updated version of the EORTC QLQ-BC23 questionnaire for assessing quality of life in breast cancer patients (abstract 1930). The final version now consists of 45 items in total, including four additional scales that cover endocrine therapy symptoms, endocrine sexual symptoms, skin mycosis symptoms and breast satisfaction. Renewed calls to clinical investors were made to consider broadening the eligibility for clinical trials concerning age. Based on analysis from clinical trials at Gustave Roussy (abstract 424P_PR) and considering that the incidence of certain cancers is increasing in Adolescents and Young Adult (AYA) populations (abstract 15590), it was proposed to the lower the age limit of 12 years in adult trials and increase the upper limit for pediatric trials to 25 years of age.
Precision medicine and NGS
Finally, key challenges in implementing precision medicine into clinical trials were highlighted through the work done at the START Early Clinical Development units in Madrid. A retrospective study was conducted between 2011 and 2017 to evaluate how tumor molecular profiling and pre-screening are implemented in early trials, where next generation sequencing (NGS) and Immunohistochemistry (IHC) are used. Out of 968 patients with an evaluable tumor sample, 294 had a positive test (molecular alteration) by NGS or IHC and of those only 90 (9.3%) patients were enrolled in a matched clinical trial. In the remaining 204 patients, 25.1% enrolled in a more readily available non-targeted clinical trial, 20.7% failed eligibility criteria, 19% received standard of care, 3% had a rapid deterioration and 2.7% did not return to the centres. Overall, 3.67% of the total 1,196 patients analyzed obtained a clinical benefit from the precision medicine approach. The authors highlighted that even though these findings are disappointing, some of the underlying causes, such as prolonged time for central laboratory testing for screening and unavailability of clinical trial slots should be possible to address. Despite their simplicity, studies like this are highly important, if not for reinforcing the key message from Josep Tabernero (ESMO president) for this year’s meeting that “sharing data, different experiences, perspectives and best practices will trigger ideas that will ultimately translate into optimal care”.
See you next year in Barcelona, OLA!