Cancer News from AACR's 2021 Meeting: Targeted Therapy and Immunotherapy

The annual meeting of the American Association for Cancer Research (AACR) is one of the largest cancer research meetings of its kind, bringing together a range of researchers, from those who spend their time in the lab to those who focus on patients in the clinic. The meeting atmosphere is electric — even when it’s virtual. Here are five key studies that stood out during the first week of the virtual AACR meeting, held April 10–15, 2021.

Lymphoma Progression Cut in Half When Rituxan Is Paired With Aliqopa

What’s new Patients with relapsed indolent non-Hodgkin lymphoma saw a 48 percent reduced risk of progression (time without the disease advancing or death) when the targeted therapy Aliqopa (copanlisib) was used in combination with Rituxan (rituximab) versus Rituxan alone. Rituxan alone is the current standard therapy for relapses. The results, which come from a phase 3 trial known as CHRONOS-3, were announced at the AACR meeting and simultaneously published in Lancet Oncology.

Study details In the CHRONOS-3 randomized controlled trial, nearly 500 patients were randomly assigned either to receive the combination of Aliqopa and Rituxan or a placebo plus Rituxan. The trial found that the average progression-free survival time with the Aliqopa/Rituxan combination was 21.5 months, versus 13.8 months with Rituxan alone. The most common side effects of the treatment were higher blood glucose (hyperglycemia) and higher blood pressure (hypertension). Neither of these side effects required treatment, and few patients were forced to stop drug therapy because of them.

Why it matters Indolent non-Hodgkin lymphoma is common, accounting for 40 percent of all non-Hodgkin lymphomas, according to the Leukemia and Lymphoma Society. The problem with Rituxan is that “it does not work as frequently or for as long as we would like,” says one of the study’s lead authors, Matthew J. Matasar, MD, of Memorial Sloan Kettering Cancer Center in New York City. Research indicates that the survival of lymphoma cells depends on a cell-signaling pathway called PI3K. Aliqopa is a PI3K inhibitor that selectively kills lymphoma cells by blocking their PI3K pathway.

RELATED: How Is Hodgkin Lymphoma Treated?

Immunotherapy Plus Chemotherapy Packs a Punch Against Earlier-Stage Lung Cancer

What’s new The immunotherapy drug Opdivo (nivolumab), when added to chemotherapy before surgery, may increase survival in patients with early-stage non-small-cell lung cancer (NSCLC). Opdivo is approved by the FDA for treatment of metastatic (cancer that has spread to other parts of the body) NSCLC. But this trial marked Opdivo’s debut for early-stage, resectable (capable of being surgically removed) NSCLC.

Study details In this trial, known as CheckMate-816, Opdivo plus chemotherapy yielded a significant improvement in pathological complete response (pCR). (Pathological complete response means that there were no signs of cancer in patients’ tissue samples.) In the study, the pCR rate in the Opdivo group was 24 percent, 10-fold higher than the rate observed with chemotherapy alone. The Opdivo group had no higher rates of treatment-related side effects than the chemotherapy group.

Why it matters Improvement of pCR is a positive development because “studies show a clear trend that patients who achieve a pCR with neoadjuvant chemotherapy [chemotherapy timed prior to surgery] live longer than those who do not,” says Patrick Forde, MBBCh, one of the study’s lead authors and a thoracic oncologist and associate professor at Sidney Kimmel Comprehensive Cancer Center and Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins University in Baltimore. “I believe that CheckMate-816 has the potential to change [the] treatment paradigm,” says Dr. Forde.

RELATED: Why Are ‘Never-Smokers’ Getting Lung Cancer?

‘Super Glue’ Protein Allows Immune System to Amp Up Response to Metastatic Ocular Melanoma

What’s new Treatment with tebentafusp, a protein that “super glues” cancer cells to T cells in the immune system, cut the risk of death from metastatic uveal melanoma, a difficult-to-treat and rare melanoma of the eye, in half compared with a control, according to research presented at the AACR.

Study details In a large phase 3 trial, nearly 375 patients with metastatic uveal melanoma were randomized to receive tebentafusp, while another 250, in the control group, were given the investigator’s choice of therapy. The average survival time after uveal melanoma has metastasized is less than one year. In the study, the tebentafusp group had almost half the risk of death as those in the other group after an average of 14 months.

Why it matters Tebentafusp enables T cells to recognize and target cancer cells. It’s a particularly welcome advance in the case of uveal melanoma, for which there is currently no standard treatment for patients in whom it has metastasized. “Tebentafusp has the potential to become a practice-changing therapy for patients with this disease,” says Jessica Hassel, MD, one of the lead authors of the study.

RELATED: Can Genetics Determine Risk for Melanoma Progression?

Men at High Genetic Risk for Prostate Cancer Can Cut Risk With a Healthy Lifestyle

What’s new A two-decade-long epidemiology study has found that men with the highest genetic risk of prostate cancer can cut their risk of getting a lethal form of the disease by 46 percent if they lead a healthy lifestyle. This finding, however, was restricted to metastatic or lethal prostate cancer, not prostate cancer overall. It was also restricted to the men with the highest level of genetic risk.

Study details The 10,443 men under study were free of prostate cancer when the study began in 1993. Over time, 2,111 of them developed prostate cancer, including 238 with lethal prostate cancer. The question was, could genetic risk of prostate cancer, which was quantified by a polygenic risk score assigned on the basis of gene analysis, be counterbalanced by a healthy lifestyle?

The investigators found that men with the highest level of genetic risk had a more than five times higher risk of overall prostate cancer and more than three times higher risk of metastatic or lethal prostate cancer when compared with the lowest level of genetic risk.

Four levels of genetic risk were compared with a lifestyle score based on six factors: (1) having a healthy weight, (2) vigorous physical activity, (3) not smoking, and high consumption of (4) tomatoes, (5) fatty fish, and (6) reduced consumption of processed meat. They found that men with the highest level of genetic risk had a lower risk of lethal prostate cancer (by 46 percent) if they adhered to a healthy lifestyle. This finding was not significant in any of the three other genetic risk groups.

Why it matters This study is an example of gene-environment interactions. One of the lead investigators, Anna Plym, PhD, of the Brigham and Women’s Hospital and the Harvard T.H. Chan School of Public Health in Boston, says the results underscore the importance of surveillance of men with a high genetic predisposition to prostate cancer and to impress upon them that genes are not necessarily destiny.

RELATED: Food as Medicine: What It Means and How to Reap the Benefits

Women With Ovarian Cancer at Risk of Mental Illness

What’s new Ovarian cancer survivors were three times more likely than women in the general public to have a mental illness diagnosis, and their mental illness diagnosis appeared to be linked to survival, according to an epidemiological study by researchers from the University of Utah in Salt Lake City.

Study details The population-based study (the gold standard for epidemiology study design) relied on the Utah Cancer Registry to find nearly 1,700 ovarian cancer survivors diagnosed between 1996 and 2012. Those survivors were matched with 7,000 women without cancer. The rate of mental illness was compared across the two groups using electronic health records. In the first two years after their cancer diagnosis, the ovarian cancer survivors were 3 times more likely to have depression, 3.5 times more likely to have anxiety disorder, and almost 4 times more likely to have adjustment disorder. Ovarian cancer survivors with a mental illness diagnosis also had an 80 percent higher risk of death than survivors without one.

Why it matters “Mental health screening among ovarian cancer patients is needed … [They] may need regular mental health consultations to identify issues such as depression and anxiety,” said lead author of the study, Siqi Hu, of the University of Utah and Huntsman Cancer Institute. “Increased support may contribute to prolonging the lives of ovarian cancer survivors,” she says.

RELATED: Ovarian Cancer: Myths vs. Facts

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