Key Takeaway
PDAC treatment dynamics have been reset by the arrival of credible KRAS inhibition - the field’s first targeted therapy to improve survival - after more than a decade defined by an entrenched chemotherapy backbone and a string of late-stage pipeline failures. Three needs stand above the rest in physician priorities: targeted therapies capable of improving overall survival without requiring addition to a chemotherapy backbone, regimens with a more tolerable side effect profile relative to standard of care, and novel mechanisms of action that can be combined with KRAS inhibition to deepen and prolong responses.
Based on in-depth interviews with seven KOLs - medical oncologists, a surgical oncologist, a radiation oncologist, and a translational researcher - across the U.S., UK, France, and Italy, REACH’s MarketVue® PDAC report maps a treatment landscape defined more by what is missing than what is working. FOLFIRINOX and gemcitabine-based regimens remain the foundation of care across all settings. Targeted approaches have failed repeatedly at the late-stage level. And a meaningful proportion of patients - those with poor performance status - are left without viable options entirely. Against this backdrop, KRAS inhibition has emerged as the first credible mechanism to break the chemotherapy ceiling, resetting both physician expectations and commercial opportunity.
Three Critical Gaps Are Anticipated in Future PDAC Care
1. Therapies That Improve OS Without Adding to Chemotherapy SOC
Surveyed oncologists consistently named the absence of a standalone targeted therapy as the single greatest gap in PDAC - not simply the lack of a drug that works, but the lack of one that works without being layered on top of an already-burdensome chemotherapy backbone. The field has lived through a series of late-stage failures that reinforced this frustration: pamrevlumab, tested in both the Precision Promise platform and the Phase 3 LAPIS trial, failed to improve OS in 2024 despite years of investment; NIS793 was discontinued by Novartis in 2023; napabucasin’s Phase 3 CanStem111P trial was terminated for futility. Against this backdrop, KRAS inhibition - long described by KOLs as the “holy grail” given mutations in over 90% of PDAC - has produced the field’s first credible signal: daraxonrasib (RMC-6236) reported Phase 3 RASolute 302 results in April 2026 showing it approximately doubled median OS as a monotherapy vs chemotherapy in previously treated metastatic PDAC, with Revolution Medicines indicating intent to file an NDA. With this new standard of care taken into account, the specific benchmarks physicians require for a novel targeted therapy to change prescribing behavior - across lines of therapy and geographies - are detailed in the full MarketVue® report.
“The holy grail obviously is sort of trying to inhibit KRAS, which is an oncogene that we see mutations in 90% of pancreatic cancers, so if you block signaling through this KRAS oncogene, and the possibility of developing more selective small molecule inhibitors against G12D or G12R or G12V is certainly an area of intense investigation as well.”— PDAC KOL
2. Treatment Options With a Better Side Effect Profile Relative to Current Chemotherapy SOC
The toxicity burden of FOLFIRINOX is not a secondary concern - it is a real barrier to treatment delivery. KOLs described patients who complete surgery but never receive adjuvant chemotherapy because they cannot recover in time, patients who require oxaliplatin dose reductions or switches due to cumulative neuropathy, and a broader population of patients who decline or discontinue treatment because the regimen simply cannot be sustained. Daraxonrasib begins to validate that a targeted monotherapy can carry a gentler burden than FOLFIRINOX - treatment-related discontinuation ran substantially lower in the Phase 3 RASolute 302 trial vs chemotherapy. The specific tolerability thresholds that physicians and patients can accept when evaluating new regimens are captured in the full MarketVue® report.
“Only about 60% of patients make it to adjuvant chemotherapy, and the other 40% don’t make it because of either surgical complications, the patients don’t want to have chemotherapy, or they just aren’t fit enough, and then out of the 60% that do go to adjuvant chemotherapy, only about half of those can keep at the full dose because of patient fitness and side effects.”— PDAC KOL
3. Novel Mechanisms of Action to Combine With KRAS Inhibition
The potential for daraxonrasib to establish KRAS inhibition as a new standard of care opens a distinct opportunity: a targeted backbone on which to build novel combinations. Responses to KRAS inhibition as monotherapy are largely partial and finite, leaving significant room for improvement. The more pressing question is which approaches KOLs see as most promising for closing that gap when combined with KRAS inhibition. Four directions stand out: stromal and microenvironment modulation, with TGF-beta and FAP among the most-cited pathways; immunotherapy combinations designed to overcome the inherent resistance of pancreatic tumors; antigen-directed approaches against claudin 18.2; and, the strategy now most active in the clinic, pairing the multi-selective backbone with a mutant-selective inhibitor. The combination strategies physicians view as most credible - and the differentiation bar a partner agent must clear to earn a place alongside a KRAS inhibitor - are detailed in the full MarketVue® report.
“TGF-beta is a very interesting pathway. It might be quite important in sort of remodeling the peritumoral microenvironment and sort of the stroma, and that’s an active area of interest.”— PDAC KOL
The Bottom Line
PDAC treatment remains one of oncology’s most difficult challenges, defined by a chemotherapy backbone that has held for over a decade and a pipeline that has delivered more late-stage failures than approvals. The KRAS inhibition story - finally moving from concept to clinical reality - represents possibly the most significant development the field has ever seen and resets the competitive landscape to highlight a new set of needs moving forward.
An overview of the new PDAC standard of care, next set of unmet needs, and approaches best suited to meet these needs reside in the full MarketVue® PDAC report. For teams evaluating their position in this space, that level of precision is where strategy becomes actionable.
About MarketVue®
MarketVue® is an opportunity assessment report that delivers KOL-informed strategic intelligence for life sciences teams operating in rare and niche disease markets. Each report integrates primary KOL research, market intelligence, and strategic analysis to answer the questions that matter most to development, commercial, and investment teams: where is and what is the size of the opportunity, what does it take to win, and how is the market about to change.