Using Immunotherapy to Treat Advanced Melanoma and Advanced Non-Small Cell Lung Cancer: The ASCO Plenary Series

The pace of progress in cancer research keeps getting faster and faster. However, the results of this research can take time to reach the medical community. The ASCO Plenary Series is a program developed by the American Society of Clinical Oncology (ASCO) to help speed the delivery of high-impact cancer research. In this series, cancer care providers gather online to learn about new, carefully selected research and discuss the study results with their colleagues.

The March 2022 session in the ASCO Plenary Series features 2 studies:

Follow the discussion about research from the ASCO Plenary Series by using the #ASCOPlenarySeries hashtag on Twitter.

Combination of nivolumab and relatlimab remains effective in slowing the growth of advanced melanoma

Who does this study affect: People with untreated advanced melanoma. 

What did this study find: A new report from the global phase II/III RELATIVITY-047 clinical trial shows that a combination of the immunotherapy drugs relatlimab and nivolumab (Opdivo) remains effective in slowing the growth of untreated advanced melanoma. The combination treatment may also shrink the melanoma and help people with this disease live longer compared with nivolumab alone.

Immunotherapy is a type of cancer treatment that boosts the body’s natural defenses to fight cancer. Nivolumab is a PD-1 immune checkpoint inhibitor that helps the body’s immune system target and destroy melanoma cells. Relatlimab is a type of immunotherapy that targets the lymphocyte-activation gene 3 (LAG-3). The LAG-3 gene controls a pathway that reduces the function of immune cells called T cells. Relatlimab releases the limits put on T cells by LAG-3. In this study, the researchers wanted to find out if targeting both PD-1 and LAG-3 pathways at the same time could slow or stop the growth of the melanoma, shrink the cancer, and help patients live longer.  

This study included 714 people from around the world with untreated melanoma that was either metastatic or could not be treated with surgery. Of the participants, 355 received the combination of relatlimab with nivolumab, and 359 received nivolumab alone. The median follow-up was just over 19 months. The median is the midpoint, meaning half of the people were followed for fewer than 19 months and the other half were followed for more than 19 months.

The study found that, in keeping with earlier results, the combination treatment slowed or stopped the cancer from growing for a median of 10.2 months, which is more than twice as long as for nivolumab alone, which was 4.6 months. The combination treatment may also help patients live longer. At 12 months, 77% of people receiving the combination treatment were still alive, compared with nearly 72% of those receiving nivolumab alone. At 24 months, nearly 64% of those receiving the combination were still alive, compared with about 58% of those receiving nivolumab.

More participants in the combination group also had their melanoma shrink or had no signs of melanoma in response to treatment. The overall response rate, which is the percentage of participants whose tumors shrank, was about 43% in the combination group compared with nearly 33% in the nivolumab alone group. Meanwhile, just over 16% of participants in the combination group had no signs of melanoma after treatment, compared with about 14% in the nivolumab alone group.

The combination treatment did cause more side effects, including serious side effects. Among those receiving the combination treatment, just over 1 in 5 experienced a serious side effect (21.1%), and 4 people died related to the treatment in this group. Of the participants who received nivolumab alone, just over 1 in 10 experienced a serious side effect (11.1%), and 2 people died related to the treatment. Side effects of any severity caused about 15% of people to stop receiving the combination treatment and about 7% of people to stop receiving nivolumab alone.  

What does this mean for patients: Supporting earlier results from this study, the combination of relatlimab and nivolumab continues to show promise as an effective first treatment for slowing or stopping the growth of advanced melanoma. It may also help people with this disease live longer.

Read this abstract and authors’ disclosures on ASCO.org.

“These findings provide additional evidence of the benefit of two checkpoints over only one and supports the combination of nivolumab and relatlimab, which had a manageable safety profile, as a potential new treatment option for patients with advanced melanoma.”

—   Georgina V. Long, MD, FRACP, PhD
Melanoma Institute Australia at the University of Sydney
Sydney, Australia

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Adding toripalimab to chemotherapy slows the growth of advanced non-small cell lung cancer and helps patients live longer

Who does this study affect: People with untreated, advanced non-small cell lung cancer (NSCLC).

What did this study find: Results from the phase III CHOICE-01 clinical trial in China show that adding the immunotherapy drug toripalimab (TuoYi) to chemotherapy in people with untreated, advanced NSCLC slowed cancer growth and helped them live longer, particularly if their tumors had certain biomarkers, which are mutations, genes, or patterns found in a tumor’s DNA.

NSCLC is the most common kind of lung cancer, and treatment for advanced NSCLC often includes immunotherapy. Toripalimab targets the PD-1 protein expressed on immune cells. PD-1 interacts with a protein called PD-L1. PD-L1 helps cancer cells hide from the immune system, and people with advanced NSCLC often have higher levels of PD-L1. By blocking the interaction between the PD-1 and PD-L1 proteins, toripalimab helps immune cells find and destroy cancer cells.

This study included 465 Chinese participants with untreated advanced NSCLC with no specific mutations, or changes, in the epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genes. Of the participants, 309 received chemotherapy with toripalimab and 156 received chemotherapy with a placebo. The median age of the participants was 63 in the toripalimab combination group and 61 in the chemotherapy plus placebo group, and the majority of participants in both groups were men.

The study found that, regardless of PD-L1 expression levels, adding toripalimab to chemotherapy stopped the cancer from growing for a median of 8.4 months, compared with 5.6 months for chemotherapy alone. At 1 year, the cancer had stopped growing in nearly 37% of participants receiving toripalimab plus chemotherapy, compared with about 17% of participants who received chemotherapy plus placebo. The toripalimab combination also helped patients live longer than those who received chemotherapy alone, but the researchers did not have enough data to calculate the difference between the 2 treatments.

The researchers also found that the toripalimab combination worked better if the cancer cells had a high overall number of gene mutations, which is called high tumor mutational burden. Among participants with cancer with a high tumor mutational burden who received toripalimab plus chemotherapy, the cancer stopped growing for a median of 13.1 months, compared with 5.5 months among those with a high tumor mutational burden who received chemotherapy alone.

Serious side effects occurred at similar rates in both groups. The most common side effects for each treatment were blood-related problems. However, more participants in the toripalimab combination group stopped treatment because of the side effects (about 14% of participants) than those receiving chemotherapy plus placebo (about 3% of participants). Serious side effects led to death among 5.5% of participants receiving the toripalimab combination, compared with 2.6% of participants in the other group.

What does this mean for patients: The combination of toripalimab with chemotherapy may help slow the growth of untreated advanced NSCLC and help people with the disease live longer, particularly if their tumors have high tumor mutational burden.

Read this abstract and authors’ disclosures on ASCO.org.

“Toripalimab plus chemotherapy represents a first-line treatment option for patients with advanced NSCLC without driver mutations.”

—   Jie Wang, MD, PhD
National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Beijing, China

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