Checkpoint inhibitors, Enhertu in spotlight as ASCO resumes in-person meetings

Researchers also dove into socio-economic disparities in cancer care

Last month in Chicago, Illinois the American Society of Clinical Oncology hosted its first in-person meeting since the COVID-19 pandemic began. In presentations and published abstracts, researchers shared a massive amount of data across all cancer types and treatment modalities. Below are just a few of the highlights from the show.

Many wins for checkpoint inhibitors

Checkpoint inhibitors are a growing class of immunotherapy drugs that use monoclonal antibodies to activate checkpoint proteins, thus helping reactivate parts of the patient’s immune system that a cancer cell has shut down. Led by Merck’s blockbuster Keytruda, these drugs have been making waves in the oncology space for some time, and this year’s ASCO kept up that trend.

For instance, a small trial of GSK’s Jemperli (dostarlimab-gxly) saw a rare 100% response rate in a small study of 12 patients with mismatch-repair deficient, locally advanced rectal cancer. At six months, all patients had no evidence of a tumour, allowing them to skip the chemotherapy and/or surgery that would normally be their next treatment.

“What’s really remarkable is this is the first time I know of in solid tumour oncology where we’ve had a 100% complete response, and we’ve completely omitted the normal standard of care,” Luis Diaz, head of the division of solid tumour oncology at Memorial Sloan Kettering and one of the doctors who designed the study, told STAT News.

As for Keytruda itself (pembrolizumab), Merck shared a number of positive results from different disease spaces, leading with the Phase 3 KEYNOTE-716 trial, which compared Keytruda to a placebo in resected stage IIB or IIC melanoma patients at a median 27.4 month follow-up. Results showed 81.2% of patients in the KEYTRUDA arm were recurrence-free at two years compared to 72.8% of patients in the placebo arm, and quality of life was comparable.

“Patients with stage IIB and IIC melanoma are at risk of seeing their cancer return and spread to distant sites,” said Dr Georgina Long, co-medical director, Melanoma Institute Australia (MIA), and chair, Melanoma Medical Oncology and Translational Research at MIA and Royal North Shore Hospital, University of Sydney, said in a statement. “The latest results from KEYNOTE-716 show the potential of pembrolizumab to help reduce distant recurrence in patients with resected stage IIB and IIC melanoma, and further highlight the important role of adjuvant therapy for these patients.”

Other notable checkpoint wins included promising early safety results for Adagene’s SAFEbody CTLA-4-inhibitor and strong Phase 3 data for Merck KGaA’s Bavencio (avelumab) PDL-1 inhibitor for kidney and bladder cancer.

Breast cancer breakthrough

The single study that seemed to receive the most buzz coming out of the show was AstraZeneca and Daichii Sankyo’s DESTINY Breast-04 study of Enhertu (trastuzumab deruxtecan). The study found that Enhertu reduced the risk of disease progression or death by 49%, whilst improving overall survival by 36% compared to chemotherapy when given as third-line treatment.

What makes the study especially impressive however, is not simply the results but the fact that they essentially create a new category of addressable breast cancer patients, those who are deemed HER2 expressing, but not HER2-positive. This was teased by some data that came out of ESMO in May, when AZ’s Sumil Verma talked to pharmaphorum about a predecessor study, the DAISY study.

“Traditionally, when we talk about HER2 targeted treatments, they work for HER2 positive breast cancer, accounting for about 15% to 20% of all breast cancer,” Verma told pharmaphorum at the time. “But up to 50% of breast cancer has what we call HER2 expression, that is traditionally not classified as HER2 positive disease, and therefore previously was not considered to be targetable. [Our data] shows that there is potential activity in not only the traditional HER2 positive patients, but also in HER2 expressing patients.”

Approval in that broader patient range could unlock $3 billion in additional sales for Enhertu, according to analysts at Credit Suisse.

For HER2 negative breast cancer patients, there was also good news from a handful of other big pharmas. A Gilead study showed that their Trodelvy (sacituzumab govitecan) could extend patient survival by 1.5 months, results that are encouraging but not necessarily clinically meaningful. Novartis’s CDK4/6 inhibitor Kisqali (ribociclib), meanwhile, saw a survival extension of 5.4 months for that same group of patients.

“Kisqali is the only CDK4/6 inhibitor to have consistently demonstrated statistically significant overall survival across its entire Phase III program,” Reshema Kemps-Polanco, executive vice president, US Oncology at Novartis, said in a statement. “Overall survival is the ultimate goal of oncology clinical trials and what patients hope for—to live longer, and to thrive. We are extremely proud of our quality of life data and that Kisqali has the longest median overall survival ever reported in HR+/HER2- metastatic breast cancer.”

New treatment avenues for multiple myeloma

As pharmaphorum’s Phil Taylor reported last month, both Janssen and Pfizer highlighted data on new BCMA-targeting bispecifics for multiple myeloma, boasting overall response rates of 63% and 60.6% respectively. Both Janssen’s teclistamab and Pfizer’s elranatamab were tested in populations of patients who had already tried many other treatments for the condition. The similar drugs on a similar timetable could lead to a rivalry when and if they secure regulatory approval.

Highlighting care disparities in pursuit of equity

Events like ASCO aren’t just about sharing the latest clinical publications. They’re also an opportunity for industry to come together for some introspection about larger trends and concerns.

The theme for ASCO this year was “Advancing Equitable Cancer Care Through Innovation” and several presentations focused on the current inequities in cancer care and clinical trials.

One study by Flatiron Health of 26,788 cancer patient records found that while telemedicine usage for cancer care increased across the board during COVID-19, its utilisation was lower for Black patients vs White patients, uninsured patients vs insured patients, rural and suburban vs urban patients, and, most dramatically, patients with lower socio-economic status, whose likelihood of using telemedicine was 10.6% vs 23.6% in the highest socio-economic groups.

Another study looked at five-year overall survival in children with neuroblastoma and found significant differences (around 10 percentage points) based on race, insurance status, and neighbourhood-level poverty.

A survey from the BECOME initiative asked 424 patients with metastatic breast cancer, 102 of whom were Black, about their feelings about clinical trials. They found that Black patients were more likely to report not having discussed clinical trials with their care teams than non-Black patients (40% vs 33%). They were also nearly twice as likely to believe unstudied treatments might be harmful.

But other studies provided some hope for correcting inequities. At least two studies looked at the effect of Medicaid expansion in the United States on cancer survival rates. One found that a 10% increase in state-level social services spending improved five-year survival for non-Hispanic Black adults and narrowed the disparity between Black and non-Black patient survival rates. Another study found that the Medicaid expansion that was offered to states as part of the Affordable Care Act was associated with a threefold increase in patients using Medicaid in cancer clinical trials.

Finally, ASCO itself released a new tool, the Interactive Map of Oncology, to help clinicians explore the interaction between COVID-19, cancer, and systemic and socio-economic factors.

“The ASCO Registry is improving the understanding of the effects of COVID-19 on treatment plans and outcomes for patients with cancer,” ASCO chief medical officer Dr Julie R. Gralow said in a statement. “This meticulous collection of data from practices across the country has already begun to inform us about commonalities and best practices across cancer types.”

Jonah Comstock

Jonah Comstock, editor-in-chief

Jonah Comstock is a veteran health tech and digital health reporter. In addition to covering the industry for nearly a decade through articles and podcasts, he is also an oft-scene face at digital health events and on digital health Twitter.

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