CYBERSPACE – For those who were looking forward to tapas on the Plaza Mayor de Madrid, there was undoubtedly a twinge of regret at participating in the European Society for Medical Oncology (ESMO) 2020 Virtual Congress from their home offices.

For others, it offered a chance to participate they might not have had otherwise.

At more than 28,000 registrations from more than 150 countries, ESMO’s Stefan Zimmermann told reporters at a press conference previewing major meeting presentations, “this virtual format is really increasing our reach.”

One of the highlights of the first presidential program was the presentation of results from the Checkmate 9ER study by Toni Choueiri, who is the director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute.

Checkmate 9ER tested the use of a combination of checkpoint blocker Opdivo (nivolumab, Bristol Myers Squibb Co.) and receptor tyrosine kinase inhibitor Cabometyx (cabozantinib, Exelixis Inc.) as first-line treatment for advanced renal cell carcinoma (RCC).

BMS and Exelixis had announced in April 2020 that the trial had met its primary endpoint of progression-free survival (PFS), as well as its secondary endpoints of improving overall survival (OS) and overall response rate (ORR), when compared to treatment with Sutent (sunitinib, Pfizer Inc.).

In the trial, the Opdivo/Cabometyx combination reduced the risk of death by 40%, and doubled PFS from 8.3 months to 16.6 months. It also expanded the ORR from 27% to 56%.

The results suggest that Opdivo and Cabometyx could join the combination of tyrosine kinase inhibitor Inlyta (axitinib, Pfizer Inc.) with either Keytruda (pembrolizumab, Merck & Co. Inc.) or Bavencio (avelumab, EMD Serono/Pfizer Inc.) as first-line treatment for advanced RCC. Opdivo is also approved in combination with CTLA-4 checkpoint blocker Yervoy (ipilimumab, Bristol Myers Squibb Co.)

Choueiri called the results “statistically significant and clinically meaningful” in his presentation.

He was enthusiastic when asked whether there are results that are statistically significant without being clinically meaningful.

“Absolutely!” Choueiri told BioWorld. “If I have a seven thousand patient trial, I will be able to tell a two week difference [in survival]. Is that meaningful? No.”

There is no equivalent of the statistical methods that decide significance to measure whether a result is meaningful or not, he acknowledged. But Choueiri pointed to the doubling of PFS as a strong indicator, as well as the fact that improvements in OS and PFS are on the order of months – “there’s no hard cutoff,” he said, “but I will tell you that weeks is not relevant.”

Another indication that treatment with Opdivo and Cabometyx meaningfully improved patients’ lot, he said, is the superior quality of life (QOL) measurements, which are gathered by asking the patients themselves about their experiences.

“When you grade toxicity, it is the doctors” indicating whether an adverse event is more or less serious, Choueiri said. For quality of life questions, “the patients rate them.”

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