Liam Davenport

August 29, 2017

MADRID — The revolution in cancer therapy represented by targeted therapy and immunotherapy will be continued at Europe's leading oncology meeting, when new data will show that the drugs are effective not only in the palliative setting but also in earlier stages of the disease.

The European Society for Medical Oncology (ESMO) 2017 Congress, which is organized by ESMO in conjunction with the European Association for Cancer Research, will take place September 8 to 12 in Madrid.

Alongside public policy sessions on issues such as escalating healthcare costs and global discrepancies in cancer outcomes, as well as patient advocacy sessions on how to involve patients in research, the program will feature 1500 original abstracts submitted by researchers from across the globe.

ESMO Congress press officer Solange Peters, MD, PhD, from the Oncology Department, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, told Medscape Medical News that the Madrid meeting is poised for a record attendance of over 23,000 delegates.

With 30% more abstracts submitted than in previous years, she said that the organizing committee had been obliged to increase the number of proffered paper sessions and presidential sessions featuring important late-breaking trials, as well as to increase the number of posters to be displayed.

Focusing on the program itself, Dr Peters said that several studies attempt to take targeted therapy and immunotherapy beyond the palliative setting of advanced disease, "with, of course, its very short expectation of survival and so on" and move them forward to an earlier stage of disease "to the curative context, to radical treatment."

Compared with the data on the same compounds presented at the ESMO Congress last year in Copenhagen, she said, the new data to be presented this year represent "a kind of a revolution, because these compounds have been developed in order to prolong survival in the palliative setting."

She added: "We are completely changing the paradigm, and the more we move, the more we can say that this will probably take over all the old guidelines and revolutionize all that we have been writing in the last decades."

One striking example is in the treatment of lung cancer. Data from the PACIFIC trial will be presented during Presidential Symposium I (September 9, 16:30 to 18:00). This study is examining the effects of the anti–programmed cell death ligand 1 (PD-L1) inhibitor durvalumab (Imfinzi, AstraZeneca) after radical radiochemotherapy in stage III non-small cell lung cancer (NSCLC).

Dr Peters explained that among patients with stage III disease, the cure rates following radiochemotherapy are typically less than 30%.

"The idea was to increase this cure rate, or the long-term benefit of the treatment, by consolidating it with durvalumab," she said. The trial sponsor, AstraZeneca, has already announced the topline result that the trial met the endpoint of increasing progression-free survival (PFS); the clinical data will now be presented at the meeting.

"Basically, I've seen the data, and it's absolutely exciting," Dr Peters added.

Another important field for adjuvant immunotherapy is that of melanoma.

Dr Peters pointed out that last year's ESMO Congress, data presented showed that the immunotherapy ipilimumab (Yervoy, Bristol-Myers Squibb) used at a 10-mg/kg dose in high-risk patients "might be a way to cure more melanoma after resection."

However, she said that "the problem is it's not reimbursed in most countries because of the cost of 10 mg/kg ipilimumab, but also because of the side effects," adding that "it's very difficult to give such a high dose of ipilimumab."

She believes, therefore, that the strategy presented at the 2016 Congress "is hardly feasible" in clinical practice. However, this year's meeting will see the presentation of CheckMate 238, during Presidential Symposium III (September 11, 16:30 to 17:45).

This trial compares standard adjuvant nivolumab (Opdivo, Bristol-Myers Squibb) treatment, given every 2 weeks, with adjuvant ipilimumab, 10 mg/kg. "This is very interesting because it would probably create the opportunity of giving an adjuvant treatment in melanoma, if nivolumab [turns out to be] better than ipilimumab," Dr Peters said.

Presidential Symposium III will also see the presentation of data on adjuvant BRAF enzyme inhibitors in melanoma. One such study is the BRIM8 trial of adjuvant vemurafenib (Zelboraf, Hoffmann-La Roche) in patients with completely resected, cutaneous BRAF mutation–positive melanoma at high risk for recurrence.

Another is the COMBI-AD trial of dabrafenib (Tafinlar, GlaxoSmithKline) in combination with trametinib (Mekinist, GlaxoSmithKline) vs two placebos in the adjuvant treatment of melanoma after surgical resection.

"So, again, trials in early disease, which is usually not really the main topic of this meeting, are trying to cure more patients with BRAF mutations in the adjuvant melanoma setting," Dr Peters said. "This is very interesting because it's moving these new strategies into early disease."

One highly anticipated presentation by the lung cancer community will be the latest central nervous system efficacy results from the ALEX study comparing alectinib (Alecensa, Genentech) with crizotinib (Xalkori, Pfizer) in patients with treatment-naive anaplastic lymphoma kinase (ALK)–positive advanced NSCLC.

As reported by Medscape Medical News, data from the study presented at the American Society of Clinical Oncology (ASCO) 2017 Annual Meeting showed that alectinib was associated with a more than doubling of the median PFS compared with crizotinib.

With these latest data from the trial to come during a Proffered Paper session at ESMO 2017 (NSCLC, metastatic; September 11, 09:15 to 10:45), Dr Peters believes that we are beginning to see that giving the latest generation of drugs as first-line therapy achieves better disease control than starting with the older, standard therapies.

"So the main conclusion in the ALK field is you should start with the best targeted therapy first," she said.

For epidermal growth factor receptor (EGFR)–mutated disease, which is the most frequent form of NSCLC, Dr Peters said that "we still don't know if it's better to sequence the drugs, like in breast cancer, one after the other…or should you give the best drug first?"

At ESMO 2016, the FLAURA investigators will tackle that question by comparing osimertinib (Tagrisso, AstraZeneca), a third-generation EGFR tyrosine kinase inhibitor (TKI), with two first-generation EGFR TKIs. Data are to be presented during Presidential Symposium I.

"AstraZenca has already stated that this trial is positive, meaning that, again, it shows that, in terms of PFS, it's better to give the best drug first as compared to the sequencing strategy," Dr Peters said.

"Of course, what is of great importance here is to see the magnitude of difference, because what you expect when you start with the best drug first is to have a PFS that is at least as good as giving the drugs sequentially."

Several trials presented at ESMO 2017 will question daily practice and challenge received wisdoms over patient follow-up. Once such is a French trial from the Intergroupe Francophone de Cancerologie Thoracique (IFCT-0302), which will be presented during Presidential Symposium I.

This study asks whether intensive follow-up of patients with lung cancer, involving routine clinic visits, chest radiography, chest computed tomography, and fiberoptic bronchoscopy to detect more small, potentially curable, recurrences and second cancers, is really necessary.

However, because this level of follow-up is included in the ASCO recommendations, the researchers felt that a large randomized study was necessary to determine the survival impact of such a strategy.

Another trial that Dr Peters highlighted is in cervical cancer. She noted that it "is a very rare disease, and we still don't really know the place of surgery."

Now, for the first time, a large, randomized trial comparing neoadjuvant chemotherapy followed by surgery with definitive, concurrent radiochemotherapy, will be presented during Presidential Symposium II (September 10, 16:30 to 18:00).

Dr Peters said that the NACTcervix trial "is not very innovative, it's not immuno, it's not molecularly directed treatment or targeted therapy, but it's really about questioning what you have been doing for the disease."

She continued: "Should you do surgery or should you do radiotherapy? This is a huge phase 3 trial, which is academic, and it's very good question."

Finally, Dr Peters highlighted that a study examining hormonal therapy in prostate cancer will be discussed in Madrid.

As reported by Medscape Medical News, at ASCO 2017 researchers presented results from the STAMPEDE and LATITUDE trials on the first-line use of abiraterone (Zytiga, Janssen) with androgen deprivation therapy, which showed significant increases in 3-year survival.

At ESMO 2017, patient-related outcomes of dual blockade of the hormonal signalling pathway from the LATITUDE trial will be presented during a Proffered Papers session (Genitourinary tumours, prostate; September 8, 14:00 to 15:30), alongside the directly randomized data from the STAMPEDE trial in prostate cancer.

For Dr Peters, refining hormonal therapy in prostate cancer "is a very important field because it questions the whole strategy in prostate cancer, in terms of keeping chemotherapy for late lines."

No funding or relevant financial relationships have been disclosed .

European Society for Medical Oncology (ESMO) 2017 Congress.  Madrid, Spain; September 8 to 12, 2017.

Follow Medscape Oncology on Twitter: @MedscapeOnc

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