ESMO and Immunotherapy by Ian Olver

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ESMO 2017 Conference Review by Professor Ian Olver AM, for oncologynews.com.au.

Almost 24,000 delegates gathered in Madrid in September for the European Society of Medical Oncology (ESMO) Annual Meeting. The theme of the conference was “Integrating Science into Oncology for a Better Patient Outcome” but this translated particularly into important updates in immunotherapy.

The initial Presidential symposium contained a report by Dr Luis Paz-Ares of the PACIFIC study. This is a randomised study of consolidation immunotherapy for at least 12 months with durvalumab (which targets PD-L1) following platinum containing chemotherapy for stage III resected non-small cell lung cancer. The progression free survival was 15.8 months for durvalumab versus 5.6 months for placebo (hazard ratio 0,52, p<0.0001). This is impressive and further studies will look at concomitant durvalumab and radiotherapy in this patient group, particularly to ascertain whether increased pulmonary toxicity will result from this approach.

In addition to single agent studies, the results of combining immunotherapy agents are being reported. The Checkmate study suggests that immunotherapy may become first-line treatment for advanced renal cell carcinoma. This phase III trial compares the standard treatment of sunitinib with combined nivolumab and ipilimumab and in poor and intermediate risk disease found a significantly improved overall survival of 26 months versus median not reached (hazard ratio 0.63, p,0.0001). The benefit was particularly observed where the tumour had high PD-L1 expression.

Likewise, this combination resulted in a survival advantage in advanced melanoma when compared to nivolumab or ipilimumab alone. With a minimum follow-up of 36 months the median overall survival had not been reached with ipilimumab and was 37.6 months in the nivolumab group and 19.9 months in the ipilimumab group (hazard ratio of the combination versus nivolumab 0.55, p<0.001).

In the third Presidential symposium, nivolumab was compared to ipilimumab when used as adjuvant therapy for resected Stage III/IV melanoma. At a median follow-up for recurrence free survival of 18.5 months, the recurrence free survival for nivolumab was 66.4% versus 52.7% for ipilimumab (hazard ratio 0.65, p<0.0001). There was less toxicity reported with nivolumab with the occurrence of grade 3 and 4 toxicities being 14% with nivolumab but 46% with ipilimumab. Of specific interest was less immune related toxicities where gastrointestinal toxicities were less with nivolumab, 2% versus 16.8% and likewise hepatic toxicities 1.8% versus 10.8%.

MASCC ESMO session with L to R Franciso Pimentel, Richard Sullivan, Ian Olver and Nathan Cherny

Sessions focussing on the range of toxicities of immunotherapies were presented in sessions such as the joint MASCC/ESMO symposium where I discussed the autoimmune toxicities and particularly the endocrinopathies and the use of steroids in alleviating them and Nathan Cherny highlighted the wider use of steroids in supportive care.

Among other studies, the MONARCH 3 trial was presented which further explores the role of cyclin dependent kinase inhibitors in in hormone receptor positive and HER2 negative disease to overcome resistance to hormones. In this study abemaciclib was added to either anastrazole or letrozole as first treatment for metastatic disease and the progression free survival versus the hormone alone was not reached versus 14.7 months (hazard ratio 0.543, p=0.000021). This benefit was particularly in more aggressive disease like those patients with liver metastases rather than good prognosis bone metastases where there was little difference between the study arms.

Although there are several other important studies with new agents, I would like to highlight a negative study which has taken 12 years to complete.

Although there are several other important studies with new agents, I would like to highlight a negative study which has taken 12 years to complete. Sudeep Gupta form Tata Memorial in Mumbai reported the results of a randomised trial in patients with stage IB to IIB squamous cell carcinoma of the cervix of conventional therapy with chemoradiotherapy versus neoadjuvant chemotherapy followed by surgery. This has global significance, particularly for low income countries without easy access to radiation therapy. Also, there is the question of whether quality of life would be improved without the radiotherapy. The trial showed that the neoadjuvant therapy and surgery was not superior to standard treatment and the chemoradiotherapy had superior disease-free survival at 5 years compared to the neoadjuvant chemotherapy and surgery of 76.7% versus 69.3% (hazard ratio 1.38, p=0.038), although there was no significant difference in overall survival. Although the question of quality of life could not be answered by this study, the toxicities of both arms of the study were acceptable. Results from an EORTC trial due next year may help resolve this issue, but in the meantime, there is no reason to change the standard chemoradiotherapy approach.

The annual ESMO meeting is growing in size and in the importance of the data being presented for the first time.

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About Author

Ian Olver

Professor Ian Olver, AM is the Professor of Translational Cancer Research and Director of the Sansom Institute for Health Research at the University of South Australia. He chairs the Australia Health Ethics Committee of NHMRC and is President of the Multinational Association of Supportive Care in Cancer. A renowned oncologist, cancer researcher and bioethicist, Ian has held senior positions in Australia and abroad. With research interests in anticancer drug studies, symptom control, bio-ethics and psycho-oncology, Ian is the author of more than 22 journal articles, 19 book chapters, has written 4 books and edited 4 others. He is a regular commentator on cancer issues in Australia and internationally.

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