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Page 8 of 12 Lo et al. J Cancer Metastasis Treat 2022;8:30 https://dx.doi.org/10.20517/2394-4722.2022.48

Table 4. NCCN (version 1.2022) definition of locally advanced pancreatic adenocarcinoma
Arterial Venous
Pancreatic head/uncinate process: • Unreconstructible SMV/PV due to tumor involvement or occlusion (can be due to tumor or
• Solid tumor contact > 180° with the SMA or CA bland thrombus)
Pancreatic body/tail:
• Solid tumor contact of > 180° with the SMA or
CA
• Solid tumor contact with the CA and aortic
involvement

CA: Celiac axis; SMA: superior mesenteric artery; SMV: superior mesenteric vein; PV: portal vein.

improved outcomes over continuing induction chemotherapy in patients with LA-PDAC is lacking and
under active investigation. A number of prospective, randomized studies were conducted to fill this
knowledge gap, and are presented below.

The phase III LAP07 RCT investigated whether adding chemoradiation to induction chemotherapy in
[18]
patients with LA-PDAC increased survival . A total of 442 patients were randomized to either gemcitabine
alone (1000 mg/m ) or in combination with erlotinib (100 mg/day) for four months, the latter being an
2
outdated multi-agent regimen by today’s standard. Patients who had stable disease or disease response
(61%; n = 269) were then randomized again to either chemoradiation with capecitabine (800 mg/m with 54
2
Gy/30 fr) or to continue induction chemotherapy alone for an additional two months. After a median
follow-up of 34.3 months, the mOS of patients receiving chemoradiation was no different from those who
continued induction chemotherapy alone (15.2 months vs. 16.5 months; HR = 1.03; 95%CI: 0.79-1.34), and
neither was mPFS. Likewise, the mOS for patients who received gemcitabine alone was no different than
patients who received multi-agent systemic therapy with erlotinib (13.6 months vs. 11.9 months; HR = 1.19;
95%CI: 0.97-1.45), and again there was no difference in mPFS. The LAP07 authors concluded that there was
no survival benefit from adding chemoradiation with capecitabine compared with continuing induction
chemotherapy alone in patients with LA-PDAC, and that there was also no survival benefit from adding
erlotinib to gemcitabine induction chemotherapy. This study supports the use of chemotherapy alone as a
neoadjuvant treatment for LA-PDAC. Notably, 18/442 (4%) patients were able to undergo curative-intent
resection, with the majority (11/18; 2% of the study population) achieving an R0 resection, 2/18 (< 1% of the
study population) achieving an R1 resection, and the remainder with unknown resection outcome. The
mOS for these 18 patients was 30.9 months, seemingly much longer than the mOS of 12.8 months in the
overall population, further providing support for the goal of being able to achieve an R0 resection as a proxy
for improved survival.

One of the first prospective studies using more standard multi-agent systemic therapy in patients with LA-
PDAC as induction was the international phase II LAPACT trial. Patients received six cycles of GnP, and
for those without disease progression, continued therapy as per investigator’s choice: continued GnP,
chemoradiation with capecitabine or gemcitabine, or surgical resection. The primary endpoint was time to
treatment failure by ITT, which is defined as the time after the first dose of study therapy until disease
progression, death by any cause, or the start of a non-protocol-defined anti-cancer therapy. Many patients
were not able to complete induction (44/107; 41%), most commonly due to AEs (22/107; 21%). Of the
62/107 (58%) patients who completed induction chemotherapy, 47/107 (44%) patients continued onto
investigator’s choice treatment: 12/107 (11%) continued GnP, 18/107 (17%) received chemoradiation, and
17/107 (16%) underwent surgical resection with 7/107 achieving an R0 resection and the remaining 10/107
achieving an R1 resection. The median time to treatment failure was 9 months for the overall population,
with a mPFS of 10.9 months, and a mOS of 18.8 months. There was no comparison of PFS or OS between
the different investigators’ choices. The disease control rate was 77.6% (83/107), with an overall response