The American Society of Clinical oncology's annual conference, widely considered the biggest meeting in cancer research, was virtual again this year, rather than on the shores of Lake Michigan in Chicago.
Results from some of the highest-profile clinical trials included in the conference arrived Thursday, ahead of the bulk of the meeting. But the many sessions throughout the weekend offered a look at several key developments, including the advance of immunotherapies into earlier lines of treatment, hyper-targeting of cancer-linked genes and cell therapy.
Read on for three storylines to watch:
A potential shift in a long-running oncology debate
More and more, immunotherapies that worked well in advanced cancers are being studied in earlier disease. Some, like Keytruda and Opdivo, are already approved for use in early skin cancer. Others could follow. Their progress is fueling a debate about a key measurement, known as disease-free survival or DFS, used to judge their success in clinical trials.
DFS assesses a drug's ability to stop cancer from returning, when a tumor can become more lethal. It's become widely used in tests in early-stage disease, and is meant to be a proxy for a treatment's ability to keep cancer patients alive longer. Ideally, a DFS benefit helps get life-saving drugs to market faster while evidence is being gathered to conclude those treatments are, in fact, extending lives.
But that hasn't always been the case, which is why many oncologists are critical of DFS. A survey conducted by analyst firm Jefferies found most lung cancer specialists were reluctant to use immunotherapies in the adjuvant setting, after surgery, until survival data are available.
Debu Tripathy, the chair of MD Anderson Cancer Center's breast medical oncology department, for instance, is wary of using immunotherapy in early cancer because of the sometimes permanent side effects the drugs can cause. "So with immunotherapy, I think we all would want to see a survival benefit," he said in an interview.
That debate was rekindled this weekend as immunotherapy studies from Roche and Merck in the adjuvant setting were presented at ASCO. In the IMpower010 study, Roche's Tecentriq reduced the risk of disease progression or death by 21% in all treated patients with early-stage non-small cell lung cancer and by 34% in those whose tumors expressed a protein predictive of a response to treatment. The number was 32% of Merck's Keytruda in Keynote-564, a test in early kidney cancer.
Both could be headed for regulatory approvals. But neither company knows, yet, whether their drugs are helping patients live longer, again leading to criticism from some oncologists on Twitter. "Disease-free survival is not a clinical endpoint. Full stop," wrote Aaron Mitchell, a medical oncologist at Memorial Sloan Kettering Cancer Center.
Still, there is some indication opinion could be changing. A snap poll of about 200 oncologists during ASCO found that while a majority would still wait for survival data before prescribing an immunotherapy, the numbers weren't overwhelming. Post-presentation discussion of IMPOWER-010, meanwhile, suggested attitudes toward the endpoint "may be shifting" as more drugs are approved based on a DFS benefit, wrote Jefferies analyst Peter Welford.
"The collective evidence supporting immunotherapy before or after surgery is becoming more compelling," wrote Jack West, a medical oncologist and lung cancer specialist at City of Hope, in an email.
Durability question hangs over NK cell therapy
ASCO provided the latest forum to examine the progress of a form of cell therapy based on natural killer or "NK" cells, a fast-emerging alternative to the T cell-based treatments that have won approvals for a handful of blood cancers.
NK cells have certain attributes that make them more convenient than the logistically complex CAR-T cell therapies, and potentially able to reach more cancers. Their developers aim to prove they're safer than T cell-based treatments, which could enable them to be used in outpatient settings, in combination regimens, or instead of "off-the-shelf" versions of CAR-T. Early results showed promise treating a form of leukemia, but it's unclear how long their effects will last compared to their T cell counterparts, and therefore, what role they'll eventually play in cancer care.
That question will likely persist following data Fate Therapeutics disclosed at ASCO. Encouragingly, the results appear comparable to CAR-T.
Eight of 11 B-cell lymphoma patients given Fate's NK cell treatment FT516 and the antibody drug rituximab in an early-stage trial responded to treatment, and six of them were driven into remission — including two who had progressed after CAR-T. Additionally, no patients had the sometimes severe neurological or immune-related side effects CAR-T recipients can experience. The most common side effects were lower counts of immune cells called neutrophils.
But Fate didn't provide any data on durability or how long the infused cells persist in the body — two of several "major uncertainties" with its NK cell treatments, wrote SVB Leerink analyst Daina Graybosch. Six-month complete responses, an important bar for effectiveness of cell therapies, will be particularly telling. Those results aren't expected until later this year.
The next battleground for targeted cancer drugs
New cancer drugs are often targeted to specific genes associated with tumors, rather than aimed broadly at the tumor's location in the body, like the lungs, breast or skin.
Drugmakers are now taking targeted treatment a step further, designing drugs tailored to specific DNA alterations within cancer-linked genes. Last month, for instance, the FDA approved a lung cancer medicine from Johnson & Johnson that targets DNA insertions in the so-called exon 20 region of a gene called EGFR. These mutations are the third most common to affect the EGFR gene, which is damaged in a significant portion of non-small cell lung cancers.
At ASCO, researchers presented new clinical trial results for similar drugs designed by the small biotech companies Cullinan Oncology and Dizal Pharma. Data from Phase 1 studies showed the drugs could shrink tumors positive for these exon 20 insertions in the EGFR gene. As the number of patients evaluated is small, it's not clear yet how the experimental drugs might eventually compare to J&J's, but initial response rates appeared to be in the same ballpark.
"We believe these data are highly competitive" with J&J's drug, known as Rybrevant, wrote SVB Leerink analyst Andrew Berens.
They may be going up against more than just J&J, however, if their drugs advance. Japan's Takeda is awaiting an FDA decision on a drug of its own that targets exon 20 insertions in EGFR for non-small cell lung cancers. A verdict from the regulator is expected by late October.