Nimotuzumab Concurrent with Gemcitabine as First-Line Treatment of Locally Advanced or Metastatic Pancreatic Adenocarcinoma

Table 5

Summary of the main results of clinical trials with anti-EGFR+chemotherapy as first-line treatment in patients with locally advanced or metastatic adenocarcinoma of the pancreas.

Study	Arms	mPFS (months)	mOS (months)	Clinical response (%)	Safety concerns	Reference
OSAG Phase IIb (Schultheis et al., 2017)	Nimotuzumab 400 mg+gem () versus gem+placebo ()	5.1 vs. 3.4 (; )	8.6 vs. 6.0; (; )	CR: -; PR: 8.6 vs. 8.6; SD: 54.8 vs. 43.0; DC: 63.0 vs. 52.0	The most frequent adverse events were fatigue (21.5% of patients, one patient grade 3), pyrexia (in 16.1%), chills (in 11.8%), and rash (in 15.1%, two patients grade 3)	[17]
NOTABLE Phase III (Qin et al., 2022)	Nimotuzumab 400 mg+gem () versus gem+placebo ()	4.2 vs. 3.6 (HR, 0.56; 95% CI, 0.12-0.99; )	10.9 vs. 8.5, (HR, 0.50; 95% CI, 0.06-0.94; )	No statistical difference in the ORR between the two groups ()	The most common grade 3 treatment-related AEs in the nim+gem group were neutropenia (11.1%), leukopenia (8.9%), and thrombocytopenia (6.7%). No grade 4 treatment-related AEs	[18]
Phase III (Phillip et al., 2010)	Cetuximab+gem () versus gem ()	3.4 vs. 3.0 (; 95% CI, 0.93 - 0.24; )	6.3 vs. 5.9 (; 95% CI, 0.91-1.23; )	CR: -; PR: 8.0 vs. 7.0; SD: 37 vs. 30; DC: 45.0 vs. 37.0; The ORR was similar in both arms of the study ()	Patients receiving cetuximab+gem: 16% of patients with grade 4-5 toxicities; 7 with grade 5 toxicities; cetuximab was associated with an increased frequency of allergic reactions and skin toxicities including acne and rash. 48% patients with grade 2-3 skin toxicities	[23]
Phase II (Ko et al., 2012)	Cetuximab+bevacizumab+gem () versus cetuximab+bevacizumab ()	3.55 vs. 1.91	5.41 vs. 4.17	CR: 3.4 vs. 0.0; PR: 10.3 vs. 3.4; SD: 31.0 vs. 24.1; DC: 44.8 vs. 27.6	Patients treated with gemcitabine experienced more grade 3–4 toxicities, including proteinuria and thromboembolic events. The study closed early due to lack of sufficient efficacy in both treatment arms	[24]
NCIC CTG PA.3 Phase III (Moore et al., 2007)	Erlotinib+gem () versus gem+placebo ()	3.75 vs. 3.55 (HR, 0.77; 95% CI, 0.64-0.92; )	6.24 vs. 5.91 (HR, 0.82; 95% CI, 0.69-0.99; )	CR+PR: 8.6 vs. 8.0; SD: 48.9 vs. 41.2; DC: 57.5 vs. 49.2 ()	Patients receiving erlotinib and Gem: higher frequencies of grade 1-2 rash, diarrhea, infection, and stomatitis. Seven patients had an interstitial lung disease- (ILD-) like syndrome possibly related to therapy	[25]
Phase II (Tai et al., 2016)	Cetuximab+bevacizumab+LGCF () versus LGCF ()	9.0 vs. 3.0 ()	10.0 vs. 7.0 ()	N/A	Targeted treatment group had a higher frequency of severe grade 3 nausea and vomiting than the conventional treatment group (74.2% vs. 7.1%, respectively)	[26]

CI: confidence interval; HR: hazard ratio; N/A: not available; ORR: objective response rate; OS: overall survival; PFS: progression-free survival; Gem: gemcitabine; LGCF: leucovorin, gemcitabine, cisplatin, and 5FU.