Ariana Pelosci

Frontline Opdivo (nivolumab) plus chemotherapy improved survival outcomes compared to chemotherapy alone for patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer or esophageal adenocarcinoma, according to research presented at the 

The median overall survival (OS), which is the time patients live before death of any cause, was 12.6 months in the combination arm compared to 10 months in the chemotherapy-alone arm. At three months, the OS rate was 83.2% versus 84.2%; at six months it was 75.8% versus 70.4%; at nine months it was 61.3% versus 56.1%, and at 12 months it was 53.3% versus 38.1% between the combination and monotherapy arms, respectively.

The median progression-free survival (PFS), which is the time patients live before their disease gets worse, was seven months in the Opdivo arm versus 5.7 months in the chemotherapy-alone arm. At six months, the PFS rate was 60.0% versus 48.2%, and at 12 months it was 20.1% versus 19.2% between the combination and monotherapy arms, respectively.

Frontline treatment with Opdivo plus chemotherapy showed improved survival outcomes for patients with advanced gastric cancer, gastroesophageal junction cancer or esophageal adenocarcinoma.

Patients given Opdivo plus chemotherapy tended to live for a median of 12.6 months, compared to 10 months for those given chemotherapy alone.

Patients in the Opdivo group also tended to live longer without their disease getting worse, compared to those given just chemotherapy.

This study, is one of the first real-world assessments since Opdivo's FDA approval in April 2021.

“This is one of the first real-world studies of (Opdivo) plus chemotherapy for the first-line treatment of advanced gastroesophageal adenocarcinoma since its approval by the FDA in April 2021,” Dr. Ian Chau, professor, and consultant medical oncologist from The Royal Marsden NHS Foundation Trust, said during the presentation at the conference.

This study enrolled 528 patients with 231 receiving Opdivo plus chemotherapy and 297 receiving chemotherapy alone. Patients received the combination or monotherapy alone between April 1, 2021, and Dec. 31, 2022.

Patients were excluded if they had received Herceptin (trastuzumab) before the start of the study treatment or an experimental drug during the study period.

Of the patients enrolled, 53.7% in the combination arm and 36.7% in the chemotherapy arm had a combined positive score (CPS) test. In patients tested for PD-L1 — the biomarker that Opdivo targets— CPS of five or more occurred in 54.8% of patients.

The median age at treatment initiation was 66 years old versus 67 years, 72.7% versus 66.7% of patients were male, and 58.9% versus 59.6% of patients were White in the Opdivo and monotherapy arms, respectively. Additionally, the most common disease between arms was gastric cancer (42.9% versus 47.1%), and most patients were diagnosed with metastatic disease (79.2% versus 69.7%) and had an ECOG performance status of 1 (34.2% versus 34.7%), indicating that they could perform most of their daily activities with no assistance.

During treatment, 37.7% of patients in the Opdivo group and 46.5% in the monotherapy group died.

The median OS for patients with a CPS of 1 or more was 15.4 months in the Opdivo arm versus 8.9 months in the chemotherapy alone arm. For those with a CPS of 5 or more, the median OS was 14.6 months in the combination arm and 8.9 months in the chemotherapy-alone arm.

Between the combination and monotherapy arms, the median PFS for patients with a CPS of less than 1 was 8.1 months, versus 5.6 months; a CPS of 1 or more was 7.5 months versus 6.3 months; a CPS of less than five was 8.1 months versus 6.1 months; and a CPS of 5 or more was 6.9 months versus 5.5 months.

Limitations to the study were also presented and included the data gathered from the Flatiron Health database as there is no complete inpatient data or medical histories outside of the oncology platform. Additionally, there is variability in monitoring and collecting data in a real-world trial versus a randomized and controlled one. The data were also collected from community practices and may not apply to academic or other settings.

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Patients with advanced gastric cancers tended to have better survival outcomes when given Opdivo plus chemotherapy, compared to those who were given chemotherapy alone. 

Adding Opdivo to Frontline Chemo Boosts Survival in Advanced GI Cancers

Durable responses were observed when Yescarta (axicabtagene ciloleucel) was used as a first-line therapy for patients with high-risk large B-cell lymphoma (LBCL), according to results from the phase 2 ZUMA-12 trial which were presented at the 

2023 American Society of Hematology (ASH) Annual Meeting and Exposition

The overall complete response (CR) rate, the study’s primary endpoint, among patients treated with Yescarta was 86%, and the partial response (PR) was 5%, translating to an objective response rate of 92%. A total of 5% of patients had stable disease and 3% had progressive disease.

It was noted that the key secondary endpoints of median duration of response (DOR), event-free survival (EFS), progression-free survival (PFS; the time a patient lives following treatment without their disease worsening) and overall survival (OS; the time a patient lives after treatment, regardless of disease status) were not reached.

“(Yescarta) may benefit patients exposed to fewer prior therapies and those with high-risk LBCL, a population with high unmet need and poor outcomes after standard first-line chemoimmunotherapy,” lead author Dr. Julio Chavez, associate member in the lymphoma section of the department of malignant hematology at Moffitt Cancer Center, said during the presentation.

The phase 2 trial included patients with high-risk LBCL with MYC and BCL2 and/or BCL6 translocations, or LBCL with an international prognostic index (IPI) score of 3 or more before enrollment. Patients also needed to have positive interim PET scans after two cycles of treatment with an anti-CD20 monoclonal antibody plus an anthracycline regimen. Additionally, they needed to be older than 18 with an ECOG performance status of 0 or 1, meaning they could perform daily activities with little or no assistance.

The median follow-up was 40.9 months with a data cutoff of May 3, 2023, assessing 40 patients. A total of 37 patients were efficacy evaluable and were given Yescarta with centrally confirmed disease type of double-hit or triple-hit lymphoma or LBCL with an IPI score of more than three. The safety analysis consisted of the 40 patients initially enrolled.

At the time of data cutoff, 73% of patients continued to have responses. A conversion from a PR to a CR occurred in 22% of patients and a stable disease to a CR in 3%.

The three-year DOR rate was 81.8%, and for patients who achieved a CR as the best response, the three-year DOR was 84.4%. The three-year EFS was 73%, for those who had a CR as a best response the rate was 84.4%.

A multivariate analysis for EFS rates found similar results and little difference among key LBCL subgroups.

For patients who achieved a CR as the best response, the three-year PFS was 84.4% and the three-year OS rate was 90.6%.

A total of 13% of patients had any treatment-emergent side effects after the primary analysis, with 8% having grade 3 or higher toxicities. Serious side effects occurred in 8% of patients.

Any infection or infestation was reported in 10% of patients with 5% having grade 3 or higher, 8% having COVID-19-related infections, 3% having device-related infections and 3% having sinusitis.

A total of eight patients died in the trial, with five having progressive disease, one from COVID-19, one from esophageal adenocarcinoma and one from septic shock. There were no reports of new cytokine release syndrome or neurologic events at any grade since the previous data cutoff. Since the primary analysis, one patient had prolonged cytopenia and this was resolved by data cutoff.

Updated safety and subgroup analyses appear consistent with previously reported results from the phase 2 ZUMA-12 study of Yescarta for patients with high-risk large B-cell lymphoma. 

Lost-Lasting Responses With Yescarta for High-Risk Large B-Cell Lymphoma

The trial found a significantly lower risk of immunohistochemistry use to detect sentinel lymph node metastases when AI was used.

Artificial intelligence (AI) may be a safe way to detect sentinel lymph nodes in patients with breast cancer while reducing the use of immunohistochemistry, recent study findings demonstrated.

Results from the CONFIDENT-B trial were presented at the 

2023 San Antonio Breast Cancer Symposium (SABCS)

According to the National Cancer Institute, the sentinel lymph node is the first lymph node to which cancer is likely to spread from the primary tumor. Immunohistochemistry is a laboratory method used to diagnose cancer and to distinguish different types of cancer. This method of diagnosis uses antibodies linked to an enzyme or fluorescent dye.

The trial found a significantly lower risk of immunohistochemistry use to detect sentinel lymph node metastases when AI was used. The involvement of AI led to a reduction in the use of immunohistochemistry in positive sentinel lymph nodes by 32%.

“Implementation of AI assistance for breast cancer sentinel lymph node assessment is safe — patients are not at risk of an inferior diagnosis,” lead study author Dr. Carmen van Dooijeweert, a clinical epidemiologist from UMC Utrecht in the Netherlands, said during the presentation. “It leads to a significant reduction of (immunohistochemistry) use and subsequent costs, it leads to a significant time reduction for pathologists, and it makes their work more enjoyable.”

The investigators on the trial aimed to determine if an AI workflow could reduce immunohistochemistry costs and maintain the standards under which they were working. A total of 190 sentinel lymph node samples were included in this analysis, with 90 in the control arm and 100 in the intervention arm. Of the available sentinel lymph node samples, 59 (31.1%) were detected to have metastases.

The pathologist's performance was analyzed, with the sensitivity (how well a test can detect a disease) increasing from 0% to 27.3% for isolated tumor cells. For micrometastases (a small number of cancer cells that spread from the primary tumor to other parts of the body), there was an increase in sensitivity from 50% to 80%. Additionally, sensitivity increased from 92.3% to 100% for macrometastases (a significant number of cancer cells that spread). The negative predictive value (the likelihood a patient with a negative test does not have the disease being tested for) of pathologists saw an increase from 78.9% to 88.2%.

This trial saw a reduction of subsequent immunohistochemistry costs by $3,200 (€3,000). In a potential future scenario involving the use of the AI algorithm, there was a predicted cost decrease of €1,500 to €3,000 per 100 sentinel lymph node samples. In another future scenario, the predicted cost reduction ranged from €7,500 to €12,500 per 100 sentinel lymph nodes.

The workflow for pathologists was also analyzed. There was a significant reduction in time in the intervention arm with an analysis of 3 minutes and 45 seconds per sample versus 6 minutes and 4 seconds in the control arm.

“What’s very important is that all pathologists stated that the algorithm was very easy to use, made their work more enjoyable and that they prefer working with the algorithm in the future,” van Dooijeweert said in the presentation.

The presentation highlighted that detecting sentinel lymph nodes is an arduous task that can become costly when immunohistochemistry stains are ordered to ensure that no metastases are missed on the original assessment. This was a single-center trial that included all consecutive sentinel lymph node samples of patients with breast cancer or in situ (in its original place) breast cancer at UMC Utrecht between September 2022 and May 2023.

Five expert breast pathologists were part of this trial and tested biweekly samples. The intervention arm used the CE-IVD-approved Metastasis Detection App by Visiopharm, and the control arm used standard practice. To ensure safety, all samples included immunohistochemistry for all morphologically negative cases.

The use of artificial intelligence to detect sentinel lymph nodes in patients with breast cancer may be able to save time and reduce costs as compared with immunohistochemistry. 

Sentinel Lymph Nodes May Be Detected With AI in Breast Cancer

Patients with newly diagnosed advanced ovarian cancer — regardless of their BRCA mutation status — tended to experience a reduction in the risk of progression or death with senaparib (IMP4297) maintenance therapy compared with placebo.

Results from the phase 3 FLAMES trial, which were presented at the 2023 European Society of Medical Oncology (ESMO) Congress showed that the median progression-free survival (PFS; time from treatment until disease worsens or death) criteria was not reached in the senaparib arm compared with 13.6 months in the placebo arm, yielding a 57% risk reduction in progression or death with senaparib. At 12 months, the PFS rate in the senaparib arm was 72.2% vs 53.7%, and at 24 months it was 63.0% vs 31.3%.

“The results support senaparib as a maintenance treatment for patients with advanced ovarian cancer after a response to first-line chemotherapy,” Dr. Xiaohua Wu, professor in the Department of Gynecology at Fudan University Shanghai Cancer Center, said during the presentation.

A total of 393 patients were enrolled and randomly to either the senaparib group (262 patients) at 100 mg each day or the matched placebo group (131 patients). Patients continued treatment for up to two years or until disease progression or unacceptable toxicity. The preplanned interim analysis data cutoff date was March 16, 2023, and the median follow-up was 22.3 months.

The primary end point was PFS by blinded independent review, with key secondary end points being PFS by investigator assessment, safety and time from randomization to discontinuation or death.

Baseline characteristics between the senaparib (271 patients) and placebo (133 patients) groups in the intent-to-treat population included a median age of 55 vs 54. Additionally, a majority had an Eastern Cooperative Oncology Group (ECOG); which determines ability of patient to tolerate therapies in serious illness performance status of 1, serous histology and a negative 


Additional patient characteristics included most having absent gross residual disease after debulking surgery in the senaparib (77.6%) and placebo groups (72.7%), a complete response to platinum-based treatment (87.5% vs 89.5%) and receipt of neoadjuvant chemotherapy (50.6% vs 51.9%). The median cycles of platinum-based treatment were 7 in both arms.

Treatment discontinuation occurred in 72.7% of patients in the senaparib arm vs 87.2% in the placebo group. Reasons for discontinuation included disease progression (30.6% vs 60.9%), completing two years of treatment (25.1% vs 16.5%), patient or investigator decision (12.5% vs 9.8%) or side effects (4.4% vs 0.0%) between both groups, respectively.

At the data cutoff, 27.3% of patients in the senaparib arm and 12.8% in the placebo arm were still receiving treatment. In the senaparib arm, the median duration of study treatment was 18.7 months vs 11.4 months in the placebo arm.

 mutation-positive, the median PFS was not evaluable in the senaparib arm vs 15.6 months in the placebo arm. For those with 

-negative disease, the median PFS was not evaluable in the senaparib arm and 12.9 months in the placebo arm.

All secondary end points showed the superiority of senaparib. The end points included median PFS by investigator assessment, median time from randomization to discontinuation or death, chemotherapy-free interval and median time from randomization to first subsequent therapy or death.

Side effects of grade 3 or higher occurred in 66.3% of patients in the senaparib arm vs 20.3% in the placebo arm, with treatment-emergent side effects being reported in 99.6% vs 97.7%, and serious side effects in 27.8% vs 3.8%. As a result of treatment-emergent side effects, dose interruptions occurred in 76.7% vs 19.5%, dose reductions in 63.3% vs 6.0%, and discontinuation in 4.4% vs 0.0% in the senaparib and placebo arms, respectively.

In the senaparib arm, the most common treatment-emergent side effects of grade 3 or higher were anemia (29 patients), thrombocytopenia (27 patients), and neutropenia (25 patients). In the placebo arm, the most common were hypertriglyceridemia (4 patients); weight increase (3 patients); and neutropenia, leukopenia and abdominal pain occurring in 2 patients each

“Senaparib demonstrated a tolerable safety profile with a very low incidence of permanent discontinuation and no significant safety concerns observed,” Wu concluded.

The phase 3 FLAMES trial showed a benefit of progression-free survival with senaparib compared to placebo in patients with newly diagnosed, advanced ovarian cancer.

Ariana Pelosci

Adding Opdivo to Frontline Chemo Boosts Survival in Advanced GI Cancers

Lost-Lasting Responses With Yescarta for High-Risk Large B-Cell Lymphoma

Sentinel Lymph Nodes May Be Detected With AI in Breast Cancer

Senaparib Improves Progression-Free Survival in Advanced Ovarian Cancer

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