Opdivo combo therapy extends survival and improves quality of life

Gastric cancer remains a representative cancer type with a poor prognosis. In the metastatic stage, the five-year relative survival rate is only 7.5 percent, significantly lower than that of breast cancer (49.0 percent) and prostate cancer (49.6 percent) at the same stage. However, the introduction of immune checkpoint inhibitors and the expansion of insurance coverage are changing the treatment paradigm.

Since September 2023, Opdivo (nivolumab) combined with chemotherapy has been reimbursed for patients with PD-L1 combined positive score (CPS) ≥5 in the first-line treatment of advanced or metastatic gastric cancer, broadening patient options. Korea Biomedical Review met with Professor Im Hyeon-su of the Department of Medical Oncology at Ulsan University Hospital to discuss the clinical benefits of this expanded coverage in practice.

Q: Advanced and metastatic gastric cancer is known to be difficult to cure. What are the key factors when establishing first-line treatment goals and strategies?

A: The ultimate goal is to extend survival. Improving quality of life is also a crucial objective. Gastric cancer patients often experience a sharp decline in quality of life immediately after diagnosis and treatment initiation. However, when a tumor responds to anticancer therapy, quality of life typically improves again.

When formulating treatment strategies, the patient’s performance status (ability to perform daily activities) is a primary consideration. Even young patients may struggle to tolerate anticancer treatment if their performance status is low. Clinical guidelines recommend conservative treatment rather than anticancer therapy for patients with poor performance status.

Furthermore, biomarkers are increasingly important in treatment selection. The likelihood of treatment response and survival extension varies significantly depending on eligibility for targeted therapies or immunotherapy.

Q: Currently, Opdivo is the only immunotherapy reimbursed in combination with chemotherapy for first-line treatment of metastatic gastric cancer. How has this expanded access changed patient care?

A: Gastric cancer, like other cancers, does not typically offer dramatic survival extensions. However, coverage of Opdivo combination therapy has extended survival for some patients and improved quality of life. Particularly significant is the shift where, in the past, new targeted therapy clinical trials often failed to deliver results, while combination immunotherapy has now established itself as the new standard of care.

Long-term responses can even lead to conversion surgery. Previously, surgery in metastatic gastric cancer was primarily palliative, performed to address feeding difficulties rather than as curative treatment. Now, conversion surgery for complete remission has become possible in cases with favorable responses to immune checkpoint inhibitors, such as isolated lymph node metastasis. These cases of long-term survival extension are increasing.

We are currently conducting a study on patients with gastric cancer who have received immunotherapy. Among them, about 50 received first-line treatment, and 60 to 70 received third-line or later therapy. Within this group, two or three patients underwent conversion surgery. It is highly encouraging that patients who were expected to have a life expectancy of only three to six months can achieve longer-term survival. The fact that these changes emerged with the introduction of immune checkpoint inhibitors is highly meaningful.

Q: In Opdivo’s approved clinical trial, the primary endpoint was evaluated in patients with PD-L1 CPS ≥5, leading to reimbursement criteria for this group. What about patients with CPS <5?

A: Even among patients with CPS <5, some show long-term responses to Opdivo. This includes those with microsatellite instability-high (MSI-H) or Epstein-Barr virus (EBV) infection, and reimbursement for this group is under discussion. Furthermore, high response rates can occur even without these markers. In fact, among my patients, there are CPS <5 cases maintaining a long-term response.

It is regrettable that coverage is still determined solely by PD-L1 CPS scores, potentially excluding patients who could benefit and gain survival advantages. CPS alone has limitations as a criterion for immune checkpoint inhibitor eligibility.

Q: Last year, updated results from the Japanese gastric cancer RWE study (G-KNIGHT) on Opdivo provided additional real-world evidence. What is the clinical significance?

A: First, it shows that anticancer treatment can be successfully attempted even in patients aged 75 or older. Of course, since this was a retrospective real-world study of patients previously treated with Opdivo, many likely had good overall health. Still, it confirmed that elderly patients can undergo active treatment if they have good functional status.

The G-KNIGHT study used Opdivo with S-1 and oxaliplatin (SOX) as first-line therapy. In Korea, based on approved indications, similar regimens are used: either oral capecitabine plus oxaliplatin (XELOX) or injectable 5-FU plus oxaliplatin (FOLFOX). FOLFOX generally shows good tolerability in elderly patients, and the study confirmed positive results with the oral regimen as well.

Regarding safety, the profile remained consistent in elderly patients even when Opdivo was added to chemotherapy. This supports the active use of Opdivo-based first-line therapy in elderly patients with good performance status. Subgroup analysis by PD-L1 CPS also showed no significant survival difference between groups, suggesting that even patients with CPS <5 can benefit from immune checkpoint inhibitors depending on their performance status or metastatic status.

Q: What areas require improvement in the overall gastric cancer treatment landscape?

A: Rapid expansion of insurance coverage is essential so more patients can benefit. While coverage is gradually expanding, many still require non-covered drugs such as targeted therapies. Faster coverage expansion is needed to prevent disparities based on financial means.

We also hope to see continued progress in treatment development. Gastric cancer was long stagnant in terms of new therapies, but in recent years several drugs, including Opdivo, have been approved as first-line treatments and reimbursed. Like breast cancer, gastric cancer patients should eventually have diverse treatment options that give them hope.

Q: What message would you emphasize to gastric cancer patients?

A: Gastric cancer severely restricts eating activities and drastically lowers quality of life, while offering limited treatment outcomes. I know patients are facing a particularly challenging time. However, I hope they spend more meaningful moments with their families during treatment. Traveling abroad is also good. I encourage them to make the most of their time.