Cancer Updates GI and Breast New Jersey: Dr Spencer’s Top Findings from the 2025 ASCO GI Cancers Symposium
Presenter:
Kristen Spencer, DO, MPH, NYU Langone Health, Perlmutter Cancer Center
Conference:
Cancer Updates GI and Breast New Jersey
Introduction
At the 2025 Cancer Updates: GI and Breast, New Jersey Conference, Dr. Kristen Spencer from NYU Langone Health, Perlmutter Cancer Center provided a review of some key findings from the 2025 ASCO Gastrointestinal Cancers Symposium, focusing on three pivotal studies:
Pancreatic Cancer: Precision Promise – Bayesian platform trial evaluating pamrevlumab plus chemotherapy in metastatic pancreatic cancer.
Hepatocellular Carcinoma: CARES-005 – Phase 2 study investigating the use of transarterial chemoembolization (TACE) combined with camrelizumab and rivoceranib in unresectable hepatocellular carcinoma (HCC).
Colorectal Cancer: BREAKWATER – Study investigating first-line use of encorafenib + cetuximab + chemotherapy in BRAF V600E-mutant metastatic colorectal cancer (mCRC).
Precision Promise: Pamrevlumab in Metastatic Pancreatic Cancer
Background: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most challenging malignancies, with poor response rates to chemotherapy and immunotherapy due in part to its dense tumor microenvironment (TME). In the Precision Promise trial, the use of pamrevlumab, an antibody targeting connective tissue growth factor, was investigated to determine if disrupting the extracellular matrix could enhance the efficacy of chemotherapy in PDAC.
Trial Design: This was a Bayesian adaptive platform trial which included fit patients with metastatic PDAC having 0–1 prior lines of therapy. The study compared pamrevlumab + gemcitabine/nab-paclitaxel (Pam + GA) versus a standard chemotherapy control arm (gemcitabine/nab-paclitaxel). The trial had a two-stage enrollment with an interim analysis conducted after 100 patients. The primary endpoint in the trial was overall survival (OS).
Key Findings: The addition of pamrevlumab to the GA regimen did not improve OS in either first (1L) or second line (2L) settings. In the 1L setting, median OS was 9.7 months for Pam + GA, as compared to 11.3 months for the control. In the 2L setting, median OS was 6.6 months for Pam + GA versus 7.8 months for the control. There was also a higher rate of treatment discontinuation in the experimental arm, as well as higher rates of fatigue, neuropathy, and hypokalemia.
Implications: Dr Spencer noted that the trial brings to light some of the challenges of targeting the stroma in PDAC, and difficulties with disrupting the tumor microenvironment as an overall therapeutic strategy. She also cited some challenges with the Bayesian trial design. Although innovative, it could be complex to implement at a wider level due to statistical and logistical hurdles. Despite the results, however, Dr Spencer emphasized “Negative studies matter”, and that, while results from the trial were negative, biomarker analyses could still provide valuable insights.
“So, what are our conclusions here? No improvement in efficacy at all… And to add insult to injury, the LAPIS trial—also using pamrevlumab—reported negative results the same day.”
CARES-005: TACE + Camrelizumab/Rivoceranib in Unresectable HCC
Background: Transarterial chemoembolization (TACE) is a standard-of-care (SOC) for intermediate-stage HCC, but Dr Spencer noted that its overall efficacy is limited. The CARES-005 trial investigated the efficacy of combining TACE with checkpoint inhibition and anti-angiogenic therapy (camrelizumab + rivoceranib) as a strategy to improve outcomes in this setting.
Trial Design: This was a multicenter, open-label, phase 2 study of patients with unresectable HCC. Patients in the trial were randomized to TACE alone (control), or TACE + camrelizumab + rivoceranib (TACE-CamRevo). The primary endpoint in the trial was progression-free survival (PFS).
Key Findings: Dr Spencer noted a significant improvement in PFS with the TACE-CamRevo combination, with a mPFS (by RECIST 1.1) of 10.8 months versus 3.2 months (HR 0.34) with TACE alone. Similarly, mPFS (using mRECIST criteria) was 8.8 months versus 3.1 months, respectively. In addition, objective response rate (ORR) rates were 61 to 65%, with a trend toward improved OS (24 versus 21.5 months), that was not statistically significant. As expected, there was a higher toxicity observed in the combination arm, particularly liver dysfunction, thrombocytopenia, and hypertension.
Implications: Dr Spencer thought the TACE-CamRevo approach was promising for select patients, but that it required further validation. She further noted the comparison to prior results for EMERALD-1, a similar trial using durvalumab/bevacizumab + TACE which also showed benefit, but with a different patient population, and a longer median PFS in the control arm. Lastly, she noted that the “PFS versus OS” debate is ongoing; while PFS was improved, the OS gain remains uncertain from the results.
“Should we care about improvements in PFS without an OS benefit? Maybe...maybe not... If it’s improving quality of life, that’s one thing… but if it’s just kicking the can down the road, that’s another.”
BREAKWATER: First-Line Encorafenib + Cetuximab + Chemo in BRAF V600E mCRC
Background: BRAF V600E-mutant metastatic CRC (mCRC) represents an aggressive patient subset with poor prognosis. Prior approvals (BEACON CRC) established the efficacy of encorafenib + cetuximab in the second line setting. The BREAKWATER study sought move this regimen into the first line setting, in combination with chemotherapy.
Trial Design: BREAKWATER was an open-label, phase 3 trial conducted in patients with previously untreated BRAF V600E mCRC. Patients in the trial were randomized to encorafenib + cetuximab + mFOLFOX6 (EC-mFOLFOX6), or to standard chemotherapy (mFOLFOX6/FOLFIRI), with the primary endpoints of progression-free survival (PFS) and overall response rate (ORR).
Key Findings: ORR was significantly improved with the encorafenib combination relative to standard chemotherapy (60.9% versus 40%). Time to response similar in both arms, but duration of response was longer with the addition of encorafenib. There was a trend toward OS improvement, but Dr Spencer noted that the data are at present immature. As expected, toxicity was somewhat higher in the EC-mFOLFOX6 arm, but events were overall manageable.
Implications: Dr Spencer viewed the data from BREAKWATER as potentially practice-changing, noting that the regimen is now standard of care for first-line treatment of BRAF V600E mCRC. She also noted two key remaining questions, first, does it matter when the regimen is given (i.e., first-line versus second line), and secondly, what would be an appropriate de-escalation strategy for these patients?
“So… my conclusion [on BREAKWATER]? This is now a first-line option. We got FDA approval in December 2024, and we’re ready to move this into prime time.”
Conclusions & Key Takeaways
Dr. Spencer concluded with her overall insights on what these studies mean for clinical practice:
Pamrevlumab failed to improve outcomes in PDAC: Results from the trial signal a need for novel approaches beyond stromal targeting.
TACE-CamRevo showed strong PFS improvement in unresectable HCC: Although OS data remains inconclusive.
BREAKWATER: Establishes encorafenib + cetuximab + chemo as a new first-line standard for BRAF V600E mCRC.
“The bottom line? The field is moving forward, but we still have a lot of unanswered questions.”
Speaker Disclosure Information: Dr Spencer reported no relevant disclosures for this presentation.