All good things must come to an end and so we reach the last day of ESMO 2016. In the opening edition of the Daily Reporter, we said our aim was to help you navigate the wealth of data in the packed Congress programme. We hope you feel that we have achieved this!
In this final edition, we wanted to share with you the Editorial Team’s personal picks of the scientific programme. At a time when clinical investigation into targeted agents in oncology is highly active, it will come as no surprise that our selection centres around this type of therapy. Some studies stood out as providing valuable guidance for the clinical community.
Giuseppe Curigliano (Editor-in-Chief): For me, a real breakthrough came in the form of a new proposal for using targeted therapy in the adjuvant setting. That is, instead of adopting a one-size-fits-all approach, we should direct therapy to those patients with clinically and/or pathologically determined high-risk disease. Impressive survival results using this approach were achieved in two placebo-controlled, phase III trials—one investigating ipilimumab following complete resection of melanoma (EORTC 18071; overall survival [OS] hazard ratio [HR] 0.72; p=0.001; Abstract LBA2_PR) and the other looking at sunitinib following nephrectomy in renal cell carcinoma (disease-free survival [DFS] HR 0.761; p=0.03; S-TRAC; Abstract LBA11_PR). These results illustrate how targeted therapies can be most effectively extended into the adjuvant setting, at least at the current time.
Floriana Morgillo (Associate Editor): I was particularly interested in the insight provided by several studies into treatment sequencing for ALK-rearranged or EGFR mutation-positive NSCLC. In ALK-rearranged disease for which crizotinib is currently the standard first-line treatment, the next-generation ALK inhibitor ceritinib prolonged progression-free survival (PFS) compared with chemotherapy (pemetrexed or docetaxel) following progression on crizotinib (HR 0.49; p<0.001) (ASCEND-5; Abstract LBA42_PR). Durable responses were seen in patients who had received multiple prior therapies, not including ALK inhibitors, with remarkable activity also in patients with brain metastases (ASCEND-3; Abstract 1208PD). In EGFR mutation-positive NSCLC, mature OS data from the LUX-Lung 7 study reported that first-line afatinib showed a non-significant trend towards a benefit over gefitinib (HR 0.86; p=0.258) (Abstract LBA43). Updated PFS and response rate (RR) analyses continued to show significant benefits for afatinib, confirming that it remains the preferred first-line choice over gefitinib.
Markus Joerger and Stefan Zimmermann (Associate Editors) both chose results from studies with checkpoint inhibitors in PD-L1-expressing NSCLC among their highlights. Arguably the most influential data here came from KEYNOTE-024, the first study of first-line pembrolizumab in patients with NSCLC and high PD-L1 expression (≥50% of tumour cells). The significant PFS (HR 0.50; p<0.001) and OS (HR 0.60; p=0.005) improvements seen with the PD-1 inhibitor over platinum-based chemotherapy (Abstract LBA8_PR) will change the future of treatment for such patients. The benefit of adding pembrolizumab to chemotherapy (carboplatin plus pemetrexed) in the first-line setting was suggested by the results of the phase I/II KEYNOTE-021 study (Abstract LBA46_PR) and this combination is likely to prove its worth in ongoing confirmatory phase III trials. Finally, the possibility of using PD-L1-directed treatment in previously treated NSCLC came closer to reality with results from the first phase III trial in this setting in which atezolizumab significantly improved OS compared with second- or third-line docetaxel (HR 0.73; p=0.0003) (OAK; Abstract LBA44_PR). We look forward to results from the ongoing CheckMate-227 (nivolumab and ipilimumab) and MYSTIC and NEPTUNE (durvalumab) studies, which are investigating potentially improved first-line immunotherapy options.
Evandro de Azambuja (Associate Editor): Amid the excitement surrounding targeted agents, I was very interested to see data urging a note of caution. While the MONALEESA-2 study confirmed the superior efficacy of ribociclib plus hormonal therapy compared with hormonal therapy alone in post-menopausal women with hormone receptor-positive breast cancer (PFS, HR 0.556; p=0.00000329) (Abstract LBA1_PR), the FALCON study reminded us that a substantial proportion of these patients will experience a long median PFS (16.6 months) with hormone therapy alone (Abstract LBA14_PR). There is an urgent need to identify biomarkers predicting the lack of efficacy of these targeted agents, thus avoiding unnecessary costs and toxicities. No less important is the worrying underreporting of adverse events with targeted agents (Abstract 320P) and the poor access to them in some parts of Europe (Abstract 1389O_PR). Also, we cannot forget that some patients will do extremely well with standard treatments and it remains our duty to identify those.
So that’s all from us for ESMO 2016! I would like to thank the Daily Reporter Editorial Team and all article contributors for their hard work in helping to put together what I think have been informative and stimulating newspaper editions. And I would like to thank you, the delegates, for taking the time to read the Daily Reporter.
We hope to see you all next year at ESMO 2017 in Madrid, Spain (8–12 September)!
This article appeared in the Tuesday edition of the Daily Reporter