2024 ASCO Direct™ Washington DC: Dr Marshall Discusses Three Key Studies in Pancreatic Cancer
Presenter:
John Marshall, MD, Georgetown University
Conference:
ASCO Direct™ Washington DC 2024
In his presentation focused on non-colorectal gastrointestinal cancer updates at the 2024 ASCO Direct™ Washington DC conference, Dr john Marshall from Georgetown University highlighted three key abstracts on pancreatic cancer, as reported at this year’s Annual Meeting of the American Society of Clinical Oncology (ASCO).
Introduction: Pancreatic Cancer - A Challenging Treatment Landscape
Pancreatic cancer remains one of the most lethal malignancies, with minimal improvements in outcomes despite extensive research. During his recent presentation at the ASCO Direct™ 2024 Conference in Washington DC, Dr John Marshall from Georgetown University reviewed three studies reported at the 2024 Annual Meeting of the American Society of Clinical Oncology (ASCO): GIANT, PASS-01, and RTOG 0848—shedding light on treatment paradigms for metastatic, resectable, and locally advanced pancreatic cancer. Dr Marshall emphasized the urgency of these ongoing efforts in pancreatic cancer, noting, “Our progress is slow. We’re starting to understand the biology, but our patients are counting on us to accelerate breakthroughs.”
GIANT – Optimizing Treatment for Older Adults
Background and Objectives
Older, and more frail patients often cannot tolerate aggressive multi-agent chemotherapy regimens used in pancreatic cancer, such as FOLFIRINOX. The GIANT (EA2186) trial compared two lesser intensity regimens: gemcitabine plus nab-paclitaxel (Gem-Nab) versus 5-fluorouracil, leucovorin, and liposomal irinotecan (Nal-IRI/5-FU) in older patients with previously untreated (treatment-naïve) metastatic pancreatic cancer.
Design and Population
Population: 176 patients aged ≥70 years, or with geriatric vulnerabilities.
Design: Randomized, phase II trial with balanced treatment arms.
Endpoints: Primary endpoint was overall survival (OS), with secondary endpoints including progression-free survival (PFS) and tolerability.
Results
Primary Outcome: Median OS was poor in both arms, and there was no significant difference between the Gem-Nab and Nal-IRI/5-FU regimen.
Secondary Outcomes: PFS and response rates were similarly unimpressive.
Adverse Events: Toxicities were overall manageable in both groups, although the frailty of the participants in the trial may have influenced the rate of early treatment discontinuation.
Dr. Marshall remarked, “The outcomes were worse than expected, raising questions about regimen selection and whether frailty indices adequately identify patients suited for treatment. We’re still not clear if three drugs are better than two in this population.”
PASS-01 – Precision Medicine in Frontline Therapy
Background and Objectives
PASS-01 (Pancreatic Adenocarcinoma Signature Stratification) explored the role of molecular profiling as a means to guide frontline therapy in pancreatic cancer. The trial aimed to determine whether gemcitabine plus nab-paclitaxel or modified FOLFIRINOX was a more effective treatment regimen, based on the molecular subtype of pancreatic tumors (either ‘classical’ or ‘basal-like’).
Design and Population
Population: 126 patients with untreated metastatic pancreatic cancer.
Design: Randomized trial comparing Gem-Nab to modified FOLFIRINOX, with extensive molecular profiling used to identify subtype.
Endpoints: Primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS) and response rates based on molecular subtype.
Results
PFS and OS: Gem-Nab showed slightly better PFS and OS as compared to the modified FOLFIRINOX regimen, although overall differences between regimens were modest.
Molecular Subtyping: ‘Classical’ type tumors appeared to respond better to both regimens, while ‘basal-like’ tumors demonstrated overall poorer outcomes. Subtype-specific survival curves, however, showed overlapping results, limiting definitive conclusions.
Adverse Events: The modified FOLFIRINOX regimen was associated with more toxicities, which was consistent with previous findings.
Dr. Marshall noted, “While PASS-01 underscores the potential of molecular stratification, we don’t yet have actionable insights. The data suggests a possible role for subtyping, but clinical implementation remains a challenge.”
RTOG 0848 – Revisiting The Need for Radiotherapy in Resected Pancreatic Cancer
Background and Objectives
The need for adjuvant (post-surgery) chemoradiation therapy in surgically treated (resected) pancreatic cancer has been a matter of debate for some time. The RTOG 0848 trial investigated the role of radiation (RT) after chemotherapy, seeking to clarify the overall impact of RT on survival.
Design and Population
Population: Patients with resected head-of-pancreas adenocarcinoma.
Design: Phase III trial with two steps:
All patients received adjuvant gemcitabine-based chemotherapy first.
Patients without disease progression were randomized to chemoradiation (5-FU/capecitabine) or to observation alone.
Endpoints: Primary endpoint was OS, with secondary endpoints including disease-free survival (DFS) and subgroup analysis according to patient’s nodal status.
Results
Primary Endpoint: Adjuvant chemoradiation did not significantly improve OS compared to observation alone.
Subgroup Analysis: While patients with node-negative disease did have a slight benefit from adjuvant radiation, the node-positive patients showed no advantage of RT.
Clinical Implications: The findings suggest a limited utility for routine post-operative radiation, particularly in patients with node-positive disease, as their disease may have already spread beyond the primary site of the tumor.
Commenting on the findings of PASS-01, Dr. Marshall noted, “We might be putting radiation oncologists out of business in pancreatic cancer. The data just doesn’t support its routine use anymore.”
Key Themes and Challenges Across Studies
Efficacy Gaps: All three studies highlighted limited efficacy for both systemic and localized pancreatic cancer treatments.
Precision Medicine Limitations: While PASS-01 demonstrated the feasibility of molecular profiling in pancreatic cancer, the study stopped short of providing any actionable clinical guidance.
Role of Radiation: RTOG 0848 reinforced a growing skepticism about the need for adjuvant radiation therapy in pancreatic cancer, particularly for node-positive patients.
Frailty Considerations: The GIANT study underscored the need for better tools to tailor regimens for frail patients.
Future Directions and Insights
Dr. Marshall called for a renewed focus on innovation in pancreatic cancers, stating, “We’re stuck comparing old regimens, with few new agents making it to the frontline. Precision medicine and translational research must accelerate to bring more effective therapies to pancreatic cancer patients.” Some of the key research priorities Dr Marshall noted included:
Enhancing molecular stratification as a means to guide personalized therapy.
Expanding biomarker-driven trials to better understand mechanisms of treatment resistance.
Reevaluating the role of radiation in the adjuvant and palliative care settings.
Conclusion
The studies highlighted by Dr Marshall from ASCO 2024 illustrate both the progress and persistent gaps in pancreatic cancer care. GIANT, PASS-01, and RTOG 0848 offer incremental insights but underscore the urgent need for transformative advances. “Pancreatic cancer remains one of our greatest challenges,” Dr. Marshall concluded. “But every study, even with modest results, brings us closer to understanding this disease and improving outcomes for our patients.”
Speaker Disclosure Information: Dr Marshall reported no relevant disclosures for this presentation.