Select Page
ASCO GI 2025

Introduction

 

The 2025 ASCO Gastrointestinal Cancers Symposium brings several potentially practice-changing advances across multiple GI malignancies.

From significant survival benefits seen with novel immunotherapy combinations in gastric and hepatocellular carcinoma, to promising results with innovative therapeutic approaches like oral paclitaxel and dual-targeting strategies, this year’s abstracts suggest we may be entering a new era of personalized treatment options.

The DRAGON-01 trial demonstrates compelling outcomes with combined intraperitoneal/intravenous paclitaxel in gastric cancer with peritoneal metastases, while long-term follow-up data from CheckMate 649 continues to reshape our approach to gastroesophageal cancers. For specialists managing GI malignancies, these findings could substantially impact clinical decision-making and patient care in the immediate future.

This report summarizes the key results and clinical implications.

Note: While we have highlighted these abstracts as potentially practice-changing based on their reported outcomes and trial design, individual clinicians should carefully evaluate the data and make treatment decisions based on their professional judgment, institutional guidelines, and each patient’s specific circumstances.

Abstract Number: 327

Intraperitoneal and intravenous paclitaxel plus S-1 versus intravenous paclitaxel plus S-1 in gastric cancer patients with peritoneal metastasis: Results from the multicenter, randomized, phase 3 DRAGON-01 trial.

Presenter: Chao Yan
Session: Oral Abstract Session A: Cancers of the Esophagus and Stomach
Keywords: NIPS, intraperitoneal paclitaxel, intravenous paclitaxel, S-1, hazard ratio, leukopenia, neutropenia, gastric cancer, peritoneal metastasis, multicenter, randomized, controlled, phase 3 trial, Kaplan-Meier survival curves, Cox regression, overall survival, toxicity, standard-of-care, clinical practice.

Abstract Summary:

  • The NIPS group (intraperitoneal and intravenous paclitaxel plus S-1) demonstrated a significantly longer median overall survival of 19.4 months compared to 13.9 months in the PS group (intravenous paclitaxel plus S-1), with a hazard ratio of 0.66 (P = 0.005).
  • One-year and two-year overall survival rates were higher in the NIPS group at 69.6% and 37.2%, respectively, compared to 54.1% and 20.3% in the PS group.
  • The most common grade 3-4 adverse events were leukopenia and neutropenia, occurring at similar rates in both groups, indicating manageable toxicity.
  • No treatment-related deaths were reported, suggesting a favorable safety profile for the NIPS regimen.
  • The study concludes that the NIPS regimen offers a significant survival benefit with manageable side effects for gastric cancer patients with peritoneal metastasis.

Clinical Importance: Practice Changing

Rationale:

    1. Strength and Reliability of the Data:
      • The study is a multicenter, randomized, controlled, phase 3 trial, which is a robust design for evaluating treatment efficacy and safety.
      • The sample size of 222 patients, with a calculated power of 80%, is adequate to detect a significant difference in overall survival, the primary endpoint.
      • The statistical analysis, including Kaplan-Meier survival curves and Cox regression, is appropriate for the data, and the results are statistically significant with a P-value of 0.005.
    2. Comparison to Current Standard-of-Care:
      • The study demonstrates a significant improvement in median overall survival for the NIPS group (19.4 months) compared to the PS group (13.9 months), with a hazard ratio of 0.66, indicating a 34% reduction in the risk of death.
      • The 1-year and 2-year overall survival rates are also notably higher in the NIPS group, suggesting a meaningful clinical benefit over the current standard regimen of intravenous paclitaxel plus S-1.
    3. Clinical Relevance and Feasibility:
      • The findings suggest that the addition of intraperitoneal paclitaxel to the standard intravenous paclitaxel plus S-1 regimen can significantly improve survival outcomes in patients with gastric cancer and peritoneal metastasis.
      • The toxicity profile is manageable, with similar rates of grade 3-4 adverse events between the two groups, and no treatment-related deaths, indicating that the regimen is feasible for clinical implementation.
      • Given the significant survival benefit and manageable safety profile, these results support the immediate incorporation of the NIPS regimen into clinical practice for this patient population.

Overall, the study provides compelling evidence that the NIPS regimen offers a superior therapeutic option for gastric cancer patients with peritoneal metastasis, warranting a change in clinical practice.

Link to Abstract 327

 


Abstract Number: 392

First-line (1L) nivolumab (NIVO) plus chemotherapy (chemo) vs chemo in patients (pts) with advanced gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma (GC/GEJC/EAC): 5-year (y) follow-up of Chinese pts from CheckMate 649.

Presenter: Lin Shen
Session: Poster Session A: Cancers of the Esophagus and Stomach and Other Gastrointestinal Cancers
Keywords: Nivolumab, chemotherapy, overall survival, progression-free survival, PD-L1 combined positive score, gastric cancer, gastroesophageal junction cancer, esophageal adenocarcinoma, objective response rate, CheckMate 649 trial, non-HER2+ gastric cancer, first-line treatment, safety profile.

Abstract Summary:

  • Nivolumab plus chemotherapy (NIVO + chemo) showed a significant overall survival (OS) and progression-free survival (PFS) benefit compared to chemotherapy alone in Chinese patients with advanced gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma, particularly in those with a PD-L1 combined positive score (CPS) ≥ 5.
  • At a 5-year follow-up, the OS rate was 24% for NIVO + chemo versus 8% for chemotherapy in patients with PD-L1 CPS ≥ 5, and 20% versus 7% in all randomized patients, indicating a sustained survival advantage.
  • The objective response rate (ORR) was higher and responses were more durable with NIVO + chemo compared to chemotherapy alone, across both PD-L1 CPS ≥ 5 and all randomized patient groups.
  • No new safety concerns were identified with extended follow-up, confirming the acceptable safety profile of NIVO + chemo.
  • These findings reinforce NIVO + chemo as a standard first-line treatment for Chinese patients with advanced non-HER2+ gastric and related cancers, aligning with previous data and global study results.

Clinical Importance: Practice Changing

Rationale:

    1. Strength and Reliability of the Data:
      • The study is a long-term follow-up (5 years) of the CheckMate 649 trial, which is a well-regarded, large-scale, randomized controlled trial. This design provides a high level of evidence.
      • The sample size of 208 Chinese patients, while a subset of the overall trial population, is substantial enough to provide reliable data specific to this demographic.
      • The statistical significance of the results is implied by the reported survival benefits and objective response rates, although specific p-values are not provided in the abstract.
    2. Comparison to Current Standard-of-Care:
      • Nivolumab plus chemotherapy has already been approved as a first-line treatment for advanced non-HER2+ gastric, gastroesophageal junction, and esophageal adenocarcinomas in China and other countries, indicating its acceptance in clinical practice.
      • The 5-year follow-up data reinforce the long-term benefits of this treatment combination, showing a significant improvement in overall survival (OS) and progression-free survival (PFS) compared to chemotherapy alone.
      • The 5-year OS rate of 24% with nivolumab plus chemotherapy versus 8% with chemotherapy alone in patients with PD-L1 CPS ≥ 5 is a substantial improvement, highlighting the treatment’s efficacy.
    3. Clinical Relevance and Feasibility:
      • The findings are directly applicable to clinical practice, particularly in China, where the study population is based. The results support the continued use of nivolumab plus chemotherapy as a standard first-line treatment.
      • The absence of new safety signals over the extended follow-up period enhances the treatment’s safety profile, making it a viable option for long-term management of these cancers.

Overall, the 5-year follow-up data from the CheckMate 649 trial provide robust evidence supporting the use of nivolumab plus chemotherapy as a first-line treatment for advanced gastric, gastroesophageal junction, and esophageal adenocarcinomas, particularly in patients with PD-L1 CPS ≥ 5. This reinforces its status as a practice-changing treatment option.

Link to Abstract 392

 


Abstract Number: 397

Efficacy of PD-1 inhibitor plus chemotherapy versus chemotherapy in advanced esophageal carcinoma: A meta-analysis of phase III clinical trials.

Presenter: Zauraiz Anjum
Session: Poster Session A: Cancers of the Esophagus and Stomach and Other Gastrointestinal Cancers
Keywords: PD-1 inhibitors, chemotherapy, objective response rate, ORR, advanced esophageal carcinoma, EC, overall survival, OS, progression-free survival, PFS, treatment-related adverse events, TRAEs, combined positive score, CPS, PD-L1 expression, first-line treatment, phase III randomized clinical trials, RCTs, random effects model, tumor histology, immunotherapy, standard-of-care, disease progression, toxicity profile.

Abstract Summary:

  • The combination of PD-1 inhibitors and chemotherapy significantly improved the objective response rate (ORR) in advanced esophageal carcinoma (EC) with an odds ratio (OR) of 2.19 compared to chemotherapy alone.
  • Overall survival (OS) was enhanced in the PD-1 inhibitor group, showing a 29% reduction in the risk of death (HR: 0.71), and progression-free survival (PFS) was also significantly better (HR: 0.62).
  • Treatment-related adverse events (TRAEs) and grade ≥3 adverse events were more frequent in the PD-1 inhibitor group, with ORs of 1.93 and 1.34, respectively.
  • Subgroup analysis indicated that patients with a combined positive score (CPS) ≥10 for PD-L1 expression experienced greater OS and PFS benefits compared to those with CPS <10.
  • The study supports PD-1 inhibitors plus chemotherapy as a first-line treatment in advanced EC, particularly in patients with high PD-L1 expression, due to its superior efficacy and manageable toxicity.

Clinical Importance: Practice Changing

Rationale:

  1. Strength and Reliability of Data:
    • The meta-analysis includes eight phase III randomized clinical trials (RCTs) with a substantial sample size of 4131 patients, which enhances the reliability and generalizability of the findings.
    • The statistical analysis demonstrates significant improvements in objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) for the PD-1 inhibitor plus chemotherapy group compared to chemotherapy alone, with robust hazard ratios and confidence intervals indicating a clear survival benefit.
    • The use of a random effects model and subgroup analyses based on combined positive score (CPS) for PD-L1 expression and tumor histology adds depth to the analysis, addressing potential heterogeneity.
  2. Comparison to Current Standard-of-Care:
    • Current standard-of-care treatments for advanced esophageal carcinoma (EC) primarily involve chemotherapy. The addition of PD-1 inhibitors represents a significant advancement, offering a 29% reduction in the risk of death and a 38% reduction in disease progression risk.
    • The findings align with emerging trends in oncology that emphasize the integration of immunotherapy with traditional chemotherapy, particularly in tumors with high PD-L1 expression (CPS ≥10).
  3. Clinical Relevance and Feasibility:
    • The results are clinically relevant, particularly for patients with a CPS ≥10, who demonstrated more pronounced benefits in OS and PFS.
    • The manageable toxicity profile, despite an increase in treatment-related adverse events (TRAEs), supports the feasibility of incorporating PD-1 inhibitors into first-line therapy for advanced EC.
    • The study provides a clear benchmark for future clinical practice and research, suggesting that PD-1 inhibitors should be considered as part of the standard treatment regimen for advanced EC, especially in patients with high PD-L1 expression.

Overall, the evidence presented in this meta-analysis is compelling enough to support a change in clinical practice, advocating for the integration of PD-1 inhibitors with chemotherapy as a first-line treatment for advanced esophageal carcinoma.

Link to Abstract 397

 


Abstract Number: 398

Nivolumab (NIVO) + chemotherapy (chemo) vs chemo as first-line (1L) treatment for advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma (GC/GEJC/EAC): 5-year (y) follow-up results from CheckMate 649.

Presenter: Yelena Janjigian
Session: Poster Session A: Cancers of the Esophagus and Stomach and Other Gastrointestinal Cancers
Keywords: Nivolumab, chemotherapy, NIVO + chemo, overall survival, progression-free survival, gastric cancer, gastroesophageal junction cancer, esophageal adenocarcinoma, programmed death ligand 1, PD-L1, combined positive score, CPS, objective response rates, ORRs, non-HER2+ gastric cancer, randomized controlled trial, RCT, blinded independent central review, BICR, CheckMate 649 trial.

Abstract Summary:

  • Nivolumab combined with chemotherapy (NIVO + chemo) demonstrated sustained overall survival (OS) and progression-free survival (PFS) benefits over chemotherapy alone in patients with advanced gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma at a 5-year follow-up.
  • The study included patients with a programmed death ligand 1 (PD-L1) combined positive score (CPS) ≥ 5, CPS ≥ 1, and all randomized patients, showing consistent OS and PFS benefits across these groups.
  • Objective response rates (ORRs) were higher and responses more durable with NIVO + chemo compared to chemotherapy alone, regardless of PD-L1 CPS status.
  • No new safety concerns were identified, confirming the acceptable safety profile of NIVO + chemo over the 5-year period.
  • These findings support the continued use of NIVO + chemo as a standard first-line treatment for advanced non-HER2+ gastric and related cancers.

Clinical Importance: Practice Changing

Rationale:

  1. Strength and Reliability of the Data:
    • The study is a large, randomized controlled trial (RCT), which is the gold standard for clinical research, involving a substantial sample size (789 patients in the NIVO + chemo group and 792 in the chemo group).
    • The follow-up period of 5 years provides robust long-term data, enhancing the reliability of the survival outcomes.
    • The use of blinded independent central review (BICR) for assessing primary endpoints (OS and PFS) adds to the credibility of the findings.
  2. Comparison to Current Standard-of-Care:
    • The study demonstrates a significant overall survival (OS) and progression-free survival (PFS) benefit of NIVO + chemo over chemotherapy alone in patients with advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma (GC/GEJC/EAC), particularly in those with PD-L1 CPS ≥ 5 and CPS ≥ 1.
    • The results are consistent with previous findings at the 4-year follow-up, reinforcing the sustained efficacy of the combination therapy.
    • The absence of new safety signals and the acceptable safety profile further support its use over standard chemotherapy.
  3. Clinical Relevance and Feasibility:
    • The findings are directly applicable to clinical practice, providing a clear advantage in terms of survival outcomes for a significant subset of patients with advanced GC/GEJC/EAC.
    • The study supports the incorporation of NIVO + chemo as a first-line treatment option, aligning with the trend towards immunotherapy-based regimens in oncology.
    • The treatment regimen is feasible, with dosing schedules (NIVO 360 mg Q3W or 240 mg Q2W) that are manageable in clinical settings.

Overall, the 5-year follow-up results from the CheckMate 649 trial provide compelling evidence for the use of nivolumab in combination with chemotherapy as a first-line treatment for advanced GC/GEJC/EAC, marking a significant advancement in the management of these cancers.

Link to Abstract 398

 


Abstract Number: 416

Outcomes of neoadjvuant chemotherapy versus chemoradiation for esophageal adenocarcinoma: A National Cancer Database analysis.

Presenter: Ravi Shridhar
Session: Poster Session A: Cancers of the Esophagus and Stomach and Other Gastrointestinal Cancers
Keywords: Neoadjuvant chemotherapy, NCT, neoadjuvant chemoradiation, NCRT, esophageal adenocarcinoma, EAC, overall survival, OS, pathologic complete responders, pathologic N0, R0 resection, adjuvant chemotherapy, National Cancer Database, NCDB, propensity score matching, PSM, survival benefit, treatment guidelines.

Abstract Summary:

  • Neoadjuvant chemotherapy (NCT) demonstrated superior overall survival (OS) compared to neoadjuvant chemoradiation (NCRT) in esophageal adenocarcinoma (EAC) patients, with median OS of 42.7 months and 5-year OS of 42% for NCT versus 34.2 months and 35% for NCRT (p = 0.001).
  • Pathologic complete responders had better outcomes with NCT, showing a median OS of 101 months and 5-year OS of 64%, compared to 71.2 months and 53% for NCRT (p = 0.04).
  • Improved mortality was linked to factors such as female gender, pathologic N0, removal of more than 10 nodes, pathologic partial or complete response, R0 resection, well/moderate grade, NCT, adjuvant chemotherapy, and higher facility volume.
  • Despite NCRT’s association with higher R0 resection and pathologic response, it did not translate into a survival benefit, suggesting a need to re-evaluate its role in treating operable EAC.
  • No survival benefit was observed with the addition of adjuvant chemoradiation.

Clinical Importance: Practice Changing

Rationale:

  1. Strength and Reliability of the Data:
    • The study utilizes a large dataset from the National Cancer Database (NCDB), which provides a robust sample size of 1007 patients in each treatment group after propensity score matching (PSM). This method helps to balance baseline characteristics and reduce selection bias, enhancing the reliability of the findings.
    • The statistical significance of the results, with a p-value of 0.001 for overall survival (OS) and 0.04 for pathologic complete responders, indicates a strong association between neoadjuvant chemotherapy (NCT) and improved survival outcomes compared to neoadjuvant chemoradiation (NCRT).
  2. Comparison to Current Standard-of-Care:
    • NCRT has been the standard of care for esophageal adenocarcinoma (EAC), but this study suggests that NCT may offer superior overall survival benefits. The median OS improvement from 34.2 months with NCRT to 42.7 months with NCT, and the 5-year OS improvement from 35% to 42%, are clinically significant.
    • The findings challenge the current paradigm and suggest that NCT could potentially replace NCRT as the preferred neoadjuvant treatment for operable EAC, warranting a re-examination of treatment guidelines.
  3. Clinical Relevance and Feasibility:
    • The study’s results are directly applicable to clinical practice, as they provide evidence that could lead to a change in treatment protocols for EAC. The improved survival outcomes with NCT, along with the lack of survival benefit from adjuvant chemoradiation, suggest a shift in treatment strategy could be beneficial for patients.
    • The feasibility of implementing NCT as a standard treatment is supported by the study’s findings, which highlight its effectiveness in a real-world, large-scale database setting.

Link to Abstract 416

 


Abstract Number: 442

Paclitaxel oral solution versus paclitaxel injection as a second-line therapy in advanced gastric cancer: A randomized, open-label, non-inferiority phase 3 trial.

Presenter: Jin Li
Session: Poster Session A: Cancers of the Esophagus and Stomach and Other Gastrointestinal Cancers
Keywords: paclitaxel oral solution, paclitaxel IV, progression-free survival, overall survival, neuropathy, alopecia, fatigue, musculoskeletal disorders, hypersensitivity reactions, neutrophil counts, white blood cell counts, treatment-related adverse events, advanced gastric cancer, randomized, open-label, non-inferiority phase 3 trial, second-line treatment, category 1 preferred regimen

Abstract Summary:

  • The study established that paclitaxel oral solution is non-inferior to paclitaxel IV in terms of progression-free survival (PFS), with a median PFS of 3.02 months for the oral solution versus 2.89 months for the IV formulation.
  • Paclitaxel oral solution demonstrated superiority in overall survival (OS), with a median OS of 9.13 months compared to 6.54 months for the IV group, indicating a 2.59-month improvement.
  • The oral solution had a more favorable safety profile, with lower incidences of neuropathy, alopecia, fatigue, and musculoskeletal disorders, and no hypersensitivity reactions without premedication.
  • The most common ≥Grade 3 treatment-related adverse events (TRAEs) were similar between groups, with slightly higher rates of decreased neutrophil and white blood cell counts in the oral group.
  • The findings support the use of paclitaxel oral solution as a viable second-line treatment option for advanced gastric cancer, offering both efficacy and a manageable safety profile.

Clinical Importance: Practice Changing

Rationale:

  1. Strength and Reliability of the Data:
    • The study is a randomized, open-label, non-inferiority phase 3 trial, which is a robust design for evaluating the efficacy and safety of a new treatment compared to the standard of care.
    • The sample size is substantial, with 536 patients enrolled, providing adequate power to detect differences in outcomes.
    • The study met its primary endpoints, demonstrating non-inferiority in progression-free survival (PFS) and superiority in overall survival (OS) for the oral solution compared to the intravenous (IV) formulation.
  2. Comparison to Current Standard-of-Care:
    • Paclitaxel IV is a category 1 preferred regimen for second-line therapy in gastric cancer. The oral solution not only met the non-inferiority criteria for PFS but also showed a statistically significant improvement in OS, with a 2.59-month increase.
    • The oral formulation offers additional benefits, such as reduced neuropathy and other adverse events, and eliminates the need for premedication and frequent hospital visits, addressing significant limitations of the IV formulation.
  3. Clinical Relevance and Feasibility:
    • The oral solution provides a more convenient administration route, potentially improving patient compliance and quality of life by reducing hospital visits and the need for intravenous access.
    • The safety profile is favorable, with lower incidences of certain adverse events, making it a viable alternative for patients who may not tolerate the IV formulation well.

Given these findings, the evidence supports the immediate incorporation of paclitaxel oral solution into clinical practice as a second-line treatment option for advanced gastric cancer, offering both efficacy and safety advantages over the current standard of care.

Link to Abstract 442

 


Abstract Number: 464

Pembrolizumab or placebo plus chemotherapy for advanced HER2-negative gastric or gastroesophageal junction (G/GEJ) adenocarcinoma: An updated analysis of KEYNOTE-859 for patients enrolled in Asia.

Presenter: Chia Jui Yen
Session: Poster Session A: Cancers of the Esophagus and Stomach and Other Gastrointestinal Cancers
Keywords: pembrolizumab, chemotherapy, overall survival, progression-free survival, objective response rate, duration of response, treatment-related adverse events, immune-mediated adverse events, HER2-negative gastric adenocarcinoma, gastroesophageal junction adenocarcinoma, phase 3 randomized controlled trial, immune checkpoint inhibitor

Abstract Summary:

  • In the Asian subgroup of the KEYNOTE-859 study, pembrolizumab plus chemotherapy significantly improved median overall survival (OS) to 17.3 months compared to 13.0 months with placebo plus chemotherapy (HR, 0.75).
  • Median progression-free survival (PFS) was also enhanced with pembrolizumab plus chemotherapy, reaching 8.4 months versus 5.8 months for the placebo group (HR, 0.72).
  • The objective response rate (ORR) was higher in the pembrolizumab group at 61.2% compared to 48.5% in the placebo group, with a longer median duration of response (DOR) of 10.0 months versus 5.8 months.
  • Grade 3-5 treatment-related adverse events were more frequent in the pembrolizumab group (59.2%) compared to the placebo group (45.4%), with immune-mediated adverse events occurring in 32.4% of pembrolizumab patients.
  • The study supports pembrolizumab plus chemotherapy as a viable first-line treatment option for advanced HER2-negative gastric or gastroesophageal junction adenocarcinoma in Asian patients, with manageable safety profiles and no new safety concerns.

Clinical Importance: Practice Changing

Rationale:

    1. Strength and Reliability of the Data:
      • The study is a global phase 3 randomized controlled trial (RCT), which is the gold standard for clinical research, providing high-quality evidence.
      • The sample size for the Asian subgroup is substantial (525 patients), enhancing the reliability of the findings.
      • The statistical significance of the results is robust, with hazard ratios (HR) for overall survival (OS) and progression-free survival (PFS) indicating a clear benefit of pembrolizumab plus chemotherapy over placebo plus chemotherapy.
    2. Comparison to Current Standard-of-Care:
      • The current standard-of-care for advanced HER2-negative gastric or gastroesophageal junction adenocarcinoma typically involves chemotherapy. The addition of pembrolizumab, an immune checkpoint inhibitor, shows a significant improvement in OS (17.3 months vs. 13.0 months) and PFS (8.4 months vs. 5.8 months), which are clinically meaningful endpoints.
      • The objective response rate (ORR) and duration of response (DOR) are also notably improved, suggesting enhanced efficacy of the combination therapy.
    3. Clinical Relevance and Feasibility:
      • The findings are directly applicable to clinical practice, particularly in Asia, where the study was conducted. The results support the use of pembrolizumab in combination with chemotherapy as a first-line treatment option for this patient population.
      • The safety profile is manageable, with no new safety signals, making the regimen feasible for clinical implementation.

Overall, the evidence from this updated analysis of the KEYNOTE-859 study is strong enough to support a change in clinical practice, recommending pembrolizumab plus chemotherapy as a new standard first-line treatment for patients with advanced HER2-negative gastric or gastroesophageal junction adenocarcinoma in Asia.

Link to Abstract 464

 


Abstract Number: 520

Nivolumab (NIVO) plus ipilimumab (IPI) vs lenvatinib (LEN) or sorafenib (SOR) as first-line (1L) therapy for unresectable hepatocellular carcinoma (uHCC): CheckMate 9DW expanded analyses.

Presenter: Masatoshi Kudo
Session: Rapid Oral Abstract Session B: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract
Keywords: nivolumab, ipilimumab, lenvatinib, sorafenib, hepatocellular carcinoma, CheckMate 9DW, overall survival, objective response rate, duration of response, Barcelona Clinic Liver Cancer stages, phase 3 randomized controlled trial, hazard ratio, p-value, standard-of-care, immunotherapy

Abstract Summary:

  • In the CheckMate 9DW study, nivolumab (NIVO) plus ipilimumab (IPI) significantly improved overall survival (OS) compared to lenvatinib (LEN) or sorafenib (SOR) in patients with unresectable hepatocellular carcinoma (uHCC), with a median OS of 23.7 months versus 20.6 months (HR 0.79, P = 0.0180).
  • The objective response rate (ORR) was notably higher with NIVO + IPI at 36% compared to 13% with LEN/SOR, and the median duration of response (DOR) was 30.4 months versus 12.9 months.
  • Subgroup analyses showed consistent survival benefits and higher ORR with NIVO + IPI across different hepatocellular carcinoma etiologies and Barcelona Clinic Liver Cancer stages.
  • Safety profiles were manageable, supporting the potential of NIVO + IPI as a standard-of-care first-line treatment for uHCC.
  • These findings reinforce the efficacy and safety of NIVO + IPI, suggesting its suitability as a first-line therapy in uHCC.

Clinical Rationale:

Practice Changing

Rationale:

  1. Strength and Reliability of the Data:
    • The study is a phase 3 randomized controlled trial (RCT), which is the gold standard for clinical research, providing high-quality evidence.
    • A substantial sample size of 668 patients enhances the reliability and generalizability of the findings.
    • The statistical significance of the results, with a hazard ratio (HR) of 0.79 for overall survival (OS) and a p-value of 0.0180, indicates a meaningful survival benefit of nivolumab plus ipilimumab (NIVO + IPI) over lenvatinib (LEN) or sorafenib (SOR).
  2. Comparison to Current Standard-of-Care:
    • The current standard-of-care for first-line treatment of unresectable hepatocellular carcinoma (uHCC) includes LEN and SOR. The study demonstrates a superior overall survival and objective response rate (ORR) with NIVO + IPI compared to these treatments.
    • The median OS improvement from 20.6 months with LEN/SOR to 23.7 months with NIVO + IPI, along with a significantly higher ORR (36% vs 13%), suggests a substantial advancement over existing therapies.
  3. Clinical Relevance and Feasibility:
    • The manageable safety profile of NIVO + IPI, as indicated by the study, supports its feasibility for clinical use.
    • The treatment regimen, involving a limited number of cycles followed by maintenance therapy, is practical and aligns with current clinical practices for immunotherapy.
    • The efficacy across various subgroups, including different etiologies of HCC and stages of disease, underscores its broad applicability in clinical settings.

Given the robust evidence of improved survival outcomes, higher response rates, and a manageable safety profile, the findings from the CheckMate 9DW study support the immediate incorporation of NIVO + IPI as a new standard-of-care option for first-line treatment of uHCC, thus classifying it as practice changing.

Link to Abstract 520

 


Abstract Number: 578

Clinical outcomes of camrelizumab + rivoceranib vs sorafenib (CARES-310) as first-line treatment for patients with unresectable hepatocellular carcinoma (uHCC) of non-viral and viral etiology.

Presenter: Rachna Shroff
Session: Poster Session B: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract
Keywords: camrelizumab, rivoceranib, sorafenib, hepatocellular carcinoma, uHCC, mOS, mPFS, non-viral, hepatitis C virus, HCV, hepatitis B virus, HBV, hypertension, AST, CARES-310, PD-1 inhibitor, VEGFR-1-3 inhibitor, adverse events, clinical trial, survival benefit, first-line treatment, practice changing, hazard ratios, p-values, safety profile, clinical guidelines

Abstract Summary:

  • The combination of camrelizumab and rivoceranib significantly improved median overall survival (mOS) and median progression-free survival (mPFS) compared to sorafenib in patients with unresectable hepatocellular carcinoma (uHCC), with mOS of 23.8 months versus 15.2 months and mPFS of 5.6 months versus 3.7 months.
  • The treatment showed a consistent survival benefit across different etiologies of uHCC, including non-viral (HR 0.68), hepatitis C virus (HCV) (HR 0.37), and hepatitis B virus (HBV) (HR 0.70) for mOS.
  • Similarly, mPFS was longer with camrelizumab plus rivoceranib across non-viral (HR 0.55), HCV (HR 0.50), and HBV (HR 0.57) etiologies.
  • The most common grade ≥3 treatment-related adverse events in the camrelizumab plus rivoceranib arm were hypertension (38.6%) and increased AST levels (20.2%).
  • The study supports the use of camrelizumab plus rivoceranib as a first-line treatment for uHCC, providing a clinically meaningful benefit regardless of the underlying etiology.

Clinical Importance: Practice Changing

Rationale:

  1. Strength and Reliability of the Data:
    • The CARES-310 study is a well-designed clinical trial comparing the combination of camrelizumab (a PD-1 inhibitor) and rivoceranib (a VEGFR-1-3 inhibitor) against sorafenib, the current standard of care for unresectable hepatocellular carcinoma (uHCC).
    • The study reports statistically significant improvements in both median overall survival (mOS) and median progression-free survival (mPFS) with the combination therapy compared to sorafenib. The hazard ratios for mOS (0.64) and mPFS (0.54) indicate a substantial reduction in the risk of death and disease progression, respectively, with p-values <0.0001, underscoring the robustness of the findings.
  2. Comparison to Current Standard-of-Care:
    • Sorafenib has been a long-standing first-line treatment for uHCC, but its efficacy is often limited. The significant improvement in survival outcomes with camrelizumab plus rivoceranib represents a major advancement over sorafenib.
    • The study demonstrates efficacy across different etiologies of HCC (non-viral, HCV, and HBV), suggesting broad applicability of the treatment regimen.
  3. Clinical Relevance and Feasibility:
    • The combination therapy not only improves survival outcomes but also provides a new therapeutic option that is effective across various etiologies of HCC, which is crucial given the diverse patient population affected by this disease.
    • The reported adverse events, such as hypertension and increased AST, are manageable and consistent with the known safety profiles of PD-1 and VEGFR inhibitors, making the regimen feasible for clinical practice.

Overall, the significant survival benefits, broad applicability across HCC etiologies, and manageable safety profile support the classification of this study as practice changing, warranting consideration for incorporation into clinical guidelines for the first-line treatment of uHCC.

Link to Abstract 578

 


Abstract Number: 652

A phase III study of combination therapy with everolimus plus lanreotide versus everolimus monotherapy for unresectable or recurrent gastroenteropancreatic neuroendocrine tumor (JCOG1901, STARTER-NET).

Presenter: Susumu Hijioka
Session: Oral Abstract Session B: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract
Keywords: everolimus, lanreotide, progression-free survival, overall survival, objective response rate, disease control rate, hematologic toxicities, non-hematologic toxicities, GEP-NETs, phase III randomized controlled trial, hazard ratio, P-value, standard-of-care, safety profile, Data and Safety Monitoring Committee

Abstract Summary:

  • The combination of everolimus plus lanreotide (EVE/LAN) significantly improved progression-free survival (PFS) compared to everolimus monotherapy (EVE), with median PFS of 29.7 months versus 11.5 months, respectively (HR 0.38, P = 0.00017).
  • Overall survival (OS) did not show a significant difference between the two groups, with a hazard ratio of 0.97.
  • The objective response rate (ORR) and disease control rate (DCR) were higher in the EVE/LAN arm (ORR: 26.8%, DCR: 91.5%) compared to the EVE arm (ORR: 8.7%, DCR: 87.0%).
  • Both hematologic and non-hematologic toxicities were more frequent in the EVE/LAN arm, but no treatment-related deaths occurred.
  • The study was recommended for early termination due to the significant efficacy of EVE/LAN, suggesting it may become a new standard first-line treatment for well-differentiated grade 1/2 GEP-NETs with poor prognostic factors.

Clinical Importance: Practice Changing

Rationale:

  1. Strength and Reliability of the Data:
    • The study is a phase III randomized controlled trial, which is a robust design for evaluating treatment efficacy.
    • The sample size, although slightly below the planned 250, is substantial with 178 patients enrolled, and the interim analysis was conducted on 145 patients.
    • The statistical significance of the primary endpoint, progression-free survival (PFS), is strong, with a hazard ratio (HR) of 0.38 and a P-value of 0.00017, which is below the prespecified significance level of 0.00046.
  2. Comparison to Current Standard-of-Care:
    • Everolimus is a well-established treatment for GEP-NETs, and the addition of lanreotide significantly improved PFS from 11.5 months to 29.7 months.
    • The improvement in PFS is substantial and clinically meaningful, suggesting a significant advancement over everolimus monotherapy.
  3. Clinical Relevance and Feasibility:
    • The combination therapy of everolimus and lanreotide shows a manageable safety profile, with no treatment-related deaths, making it feasible for clinical practice.
    • The study’s early termination recommendation by the Data and Safety Monitoring Committee due to efficacy further supports the robustness of the findings.

Given the significant improvement in PFS, the manageable safety profile, and the recommendation for early termination due to efficacy, the findings suggest that the combination of everolimus and lanreotide could be considered a new standard treatment in the first-line setting for patients with well-differentiated grade 1/2 GEP-NETs with poor prognostic factors. This positions the study as practice changing.

Link to Abstract 652

 


FOR EDUCATIONAL AND INFORMATIONAL PURPOSES ONLY

The information provided in or through this website is for educational and informational purposes only and solely as a self-help tool for your own use.

MEDICAL DISCLAIMER

The content presented on this website, including articles, text, images, videos, and all other materials, is intended solely for general informational and educational purposes. This information does not constitute medical advice and should not be relied upon for making health decisions.

Nothing on this website should be interpreted as a recommendation for medical diagnosis, treatment, or care. The information provided is not a substitute for professional medical expertise. Only qualified healthcare providers who are familiar with your individual medical history can provide personalized medical advice.

Before starting any new treatment, medication, exercise program, or making changes to your current healthcare routine, always consult with your doctor or qualified healthcare provider. Do not postpone seeking professional medical attention or disregard medical advice based on information found on this website.

Your healthcare provider, who knows your medical history, current conditions, and medications, is best positioned to give you proper medical guidance. In case of a medical emergency, contact your doctor immediately or seek emergency medical services.