ASCO 2021's Best Trials Proved We Can Do More With Less

Mark A. Lewis, MD


July 14, 2021

This transcript has been edited for clarity.

This is Dr Mark Lewis for Medscape. I'm recording this video in June 2021, when earlier this month we convened our largest oncology conference of the year, the American Society of Clinical Oncology (ASCO) annual meeting.

This year it was again necessary to hold the meeting virtually. But whether ASCO is online or in person, it's always a meeting I really look forward to because I suspect — and was again proven right — that there will be advances I can almost immediately apply to my patients' betterment. Sometimes at these meetings they ask, "How is this going to change your practice when you go back to clinic?" Once again this year, I can say that there were things that immediately changed the way I approach patient care.

For me, the theme of this year's meeting was "less is more," or at the very least, "less is noninferior." I think our paradigm in oncology for a very long time, and possibly dating back to Sidney Farber, was that we do not want to miss an opportunity to cure our patients. Ergo, we tended to err on the side of treating with large, multiagent regimens, usually with cytotoxic agents. In recent years, we've been trying to pare back the strength, intensity, and toxicity of those regimens, especially as other agents like immunotherapy enter the arena.

ASCO Accentuates the 'Negative' Trials

But I want to start by applauding the ASCO meeting organizers. This was yet another year where they took the largest spotlight of the plenary session and applied it to a "negative" study, meaning a study where we found that we could subtract or lessen treatment with no difference in outcome other than reducing toxicity and adverse effects for our patients.

As a gastrointestinal (GI) oncologist, the IDEA Trial still resonates with me. In that trial for low-risk stage III colon cancer, we learned that we could essentially halve the exposure to oxaliplatin and cut subsequent risk for neuropathy by two thirds in certain patients. That was a trial that immediately changed my view.

That happened again at this year's ASCO in a different field than mine, gynecologic oncology. The OUTBACK Trial showed that for patients with cervical cancer being treated upfront with curative-intent chemoradiation, there was no advantage to adjuvant chemotherapy in the form of carboplatin and paclitaxel. Our ability to now subtract chemotherapy from the treatment of these women without, it seems, any subsequent decrement in their cancer-related outcomes is really a triumph.

KEYNOTE-177 and CheckMate 648

Returning to the field of GI oncology, I saw several other studies reporting that immunotherapy was moving up the lines of treatment, and in some select places, displacing chemotherapy altogether. We already had a sense from the KEYNOTE-177 Trial that select microsatellite-instability–high metastatic colorectal cancer patients can receive their first-line treatment with pembrolizumab and potentially circumvent chemotherapy altogether.

Now, that is not a one-size-fits-all strategy. I think we still need to be very careful about those patients who are on the brink of visceral crisis and require a cytoreduction up front. But these survival curves for immunotherapy tend to have very long tails. If we can get our patients there without the cumulative toxicities of, for example, platinum-based chemo, that is a huge step forward.

Possibly the most amazing thing I saw in GI oncology at this year's ASCO was the CheckMate 648 trial, where the combination of nivolumab and ipilimumab upfront for the treatment of esophageal squamous cell carcinoma outperformed chemotherapy in terms of survival. It has to be said, however, that the nivolumab chemotherapy combination did best of all in terms of survival.

Sometimes these patients come to us so sick that it's hard to imagine them tolerating traditional cytotoxics. To have these chemo-free, immunotherapy-only approaches is really remarkable and, frankly, not something I thought I would see in my career.

What a time to be taking care of these patients. We have miles to go before we sleep, of course. We aren't seeing nearly enough remissions. We still sometimes sacrifice quality of life on the altar of longevity. But we are making progress. And again, kudos to ASCO for highlighting those clinical contexts where we can do a little bit less damage and still help our patients.

This is Mark Lewis, signing off for Medscape.

Mark A. Lewis, MD, is director of gastrointestinal oncology at Intermountain Healthcare in Salt Lake City, Utah. He has an interest in neuroendocrine tumors, hereditary cancer syndromes, and patient-physician communication.

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