Panitumumab in Combination With Preoperative Radiation Therapy in Patients With Locally Advanced RAS Wild-type Rectal Cancer: Results of the Multicenter Explorative Single-Arm Phase 2 Study NEORIT

The Addition of EGFR Inhibitors in Neoadjuvant Therapy for KRAS-Wild Type Locally Advanced Rectal Cancer Patients: A Systematic Review and Meta-Analysis

“…3,494 records were retrieved after database search and manual screening of references; 1,686 duplicates were removed leaving 1,808 records to proceed on title and abstract screening. 20 potential candidates underwent full-text review, of which 10 ( Bengala et al, 2009;Pinto et al, 2011;Dewdney et al, 2012;Sun et al, 2012;Helbling et al, 2013;Liang et al, 2017;Hasegawa et al, 2017;Merx et al, 2017;Leichman et al, 2018;Pinto et al, 2018)were adequate for eligibility, after excluding 10 studies which were deemed inadequate because they did not focus on KRAS-wild type LARC patients (shown in Figure 1). Among the eligible studies, six (Bengala et al, 2009;Dewdney et al, 2012;Sun et al, 2012;Liang et al, 2017;Hasegawa et al, 2017;Leichman et al, 2018) focus on the efficacy of cetuximab while the other four (Pinto et al, 2011;Helbling et al, 2013;Merx et al, 2017;Pinto et al, 2018) panitumumab.…”

“…20 potential candidates underwent full-text review, of which 10 ( Bengala et al, 2009;Pinto et al, 2011;Dewdney et al, 2012;Sun et al, 2012;Helbling et al, 2013;Liang et al, 2017;Hasegawa et al, 2017;Merx et al, 2017;Leichman et al, 2018;Pinto et al, 2018)were adequate for eligibility, after excluding 10 studies which were deemed inadequate because they did not focus on KRAS-wild type LARC patients (shown in Figure 1). Among the eligible studies, six (Bengala et al, 2009;Dewdney et al, 2012;Sun et al, 2012;Liang et al, 2017;Hasegawa et al, 2017;Leichman et al, 2018) focus on the efficacy of cetuximab while the other four (Pinto et al, 2011;Helbling et al, 2013;Merx et al, 2017;Pinto et al, 2018) panitumumab. Concerning the country/ district where these trials were conducted, three (Bengala et al, 2009;Pinto et al, 2011;Pinto et al, 2018) were in Italy, one (Merx et al, 2017) in Germany, one (Helbling et al, 2013) in Switzerland & Hungary, one (Dewdney et al, 2012) in the United Kingdom, Spain & Sweden, one (Leichman et al, 2018) in the United States of America, one (Sun et al, 2012) in the mainland of China, one (Liang et al, 2017) in Taiwan, and one (Hasegawa et al, 2017) in Japan.…”

“…Among the eligible studies, six (Bengala et al, 2009;Dewdney et al, 2012;Sun et al, 2012;Liang et al, 2017;Hasegawa et al, 2017;Leichman et al, 2018) focus on the efficacy of cetuximab while the other four (Pinto et al, 2011;Helbling et al, 2013;Merx et al, 2017;Pinto et al, 2018) panitumumab. Concerning the country/ district where these trials were conducted, three (Bengala et al, 2009;Pinto et al, 2011;Pinto et al, 2018) were in Italy, one (Merx et al, 2017) in Germany, one (Helbling et al, 2013) in Switzerland & Hungary, one (Dewdney et al, 2012) in the United Kingdom, Spain & Sweden, one (Leichman et al, 2018) in the United States of America, one (Sun et al, 2012) in the mainland of China, one (Liang et al, 2017) in Taiwan, and one (Hasegawa et al, 2017) in Japan. The detailed baseline characteristics and data of the endpoints of interest of the included studies are shown in Table 1.…”

“…Five cohorts (Pinto et al, 2011;Helbling et al, 2013;Merx et al, 2017;Leichman et al, 2018;Pinto et al, 2018) reported on Grade 3/4 diarrhea, three (Pinto et al, 2011;Helbling et al, 2013;Leichman et al, 2018) reported on Grade 3/4 hand-foot syndrome, and five (Pinto et al, 2011;Helbling et al, 2013;Merx et al, 2017;Leichman et al, 2018;Pinto et al, 2018) reported on Grade 3/4 acneiform rash. The pooled estimates of Grade 3/4 diarrhea, Grade 3/4 hand-foot syndrome, Grade 3/4 acneiform rash were 17% (95% CI, 4-34%; I 2 = 93.3%), 2% (95% CI, 0-5%; I 2 = 13.7%), and 15% (95% CI, 9-22%; I 2 = 65.4%), respectively (Figure 4).…”

“…In another RCT (SAKK 41/07), a pCR of 10% was reached in KRAS wild-type LARC patients treated with panitumumab and capecitabine compared with 18% in those treated with capecitabine. Of note, the cetuximab/panitumumab arms in these RCTs were included in this systematic review and metaanalysis, while the other eight included studies are either singlearm phase II clinical trials (Bengala et al, 2009;Pinto et al, 2011;Dewdney et al, 2012;Sun et al, 2012;Hasegawa et al, 2017;Merx et al, 2017;Leichman et al, 2018;Pinto et al, 2018) 7or single arm retrospective study (Liang et al, 2017) (1). On account of the single arm nature of the ten included cohorts and the widely-acknowledged prognostic role of pCR, we decided to conduct a single arm meta-analysis using pCR as primary endpoint to evaluate the efficacy of neoadjuvant EGFR inhibitors in LARC patients.…”