Median follow-up was ≥ 44.4 months. Median OS was increased by 3.9 months (hazard ratio 0.85 [95% confidence intervals, 0.72-0.99]) and median PFS by 1.3 months (hazard ratio 0.73 [95% confidence intervals, 0.62-0.85]) in the pertuzumab vs. the placebo arm. ORR was numerically higher (57.0% vs. 48.6%) and median DoR 1.8 months longer with pertuzumab treatment...evidence of treatment activity and an acceptable safety profile for pertuzumab plus trastuzumab and chemotherapy in previously untreated HER2-positive metastatic gastric or gastroesophageal junction cancer after long-term follow-up.

CONTRADICTING EVIDENCE: In JACOB (NCT01774786), a double-blind, placebo-controlled, randomised, multicentre, phase III study in patients (pts) with HER2-positive mGC/GEJC, addition of P to H + CT did not significantly improve overall survival (OS) v placebo (PLA) at >24.4 months (m) median follow-up; median OS: 17.5 m with P + H + CT v 14.2 m with PLA + H + CT, HR 0.84 (95% CI 0.71, 1.00); p=0.057.

Pts with HER2+ resectable EGA (≥ cT2 or cN+) were enrolled...The pCR rate was significantly improved with tras/per (A, 12%; B, 35%; p = 0.02)...DFS and OS rates [with 95% CI] at 24 months were 54% [38-71%] and 77% [63-90%] in arm A and 70% [55-85%] and 84% [72-96%] in arm B, respectively.

NON-SUPPORTIVE EVIDENCE:...overall survival was not significantly different between treatment groups (median overall survival 17·5 months [95% CI 16·2-19·3] in the pertuzumab group and 14·2 months [12·9-15·5] in the control group; hazard ratio 0·84 [95% CI 0·71-1·00]; p=0·057)....pertuzumab to trastuzumab and chemotherapy did not significantly improve overall survival in patients with HER2-positive metastatic gastric or gastro-oesophageal junction cancer compared with placebo.

pertuzumab/trastuzumab (Phesgo) is accepted for restricted use within NHSScotland....In combination with chemotherapy in...the neoadjuvant treatment of adult patients with HER2-positive, locally advanced, inflammatory, or early stage breast cancer at high risk of recurrence...In combination with docetaxel in adult patients with HER2-positive metastatic or locally recurrent unresectable breast cancer, who have not received previous anti-HER2 therapy or chemotherapy for their metastatic disease.

...Centralized detection of either an adenocarcinoma with HER-2 3+ (IHC) or HER-2 2+ (IHC) with amplification proven by FISH, SISH or CISH...Phase II/III: Subgroup analyses: pathological response according to HER-2 status HER-2 IHC 3+ vs. other cases...Phase II/III: Subgroup analyses: PFS according to HER-2 status HER-2 IHC 3+ vs. other cases...Phase II/III: Subgroup analyses: OS according to HER-2 status HER-2 IHC 3+ vs. other cases...

PETRARCA is a multicenter, randomized, investigator initiated trial planned as a phase II/III study. We report the phase II part of this trial. Pts with HER2+ resectable EGA (≥ cT2 or cN+) were randomized 1:1 to 4 pre- and post-operative cycles of FLOT (Docetaxel 50 mg/m2; Oxaliplatin 85 mg/m2; Leucovorin 200 mg/m2; 5-FU 2600 mg/m2, q2w) (Arm A) or the same regimen with tras 8/6 mg/kg and per 840 mg q3w, followed by 9 cycles tras/per (arm B). Primary endpoint for the phase II part was the rate of pathological complete remission (pCR)...The addition of tras/per to perioperative FLOT significantly improved pCR and nodal negativity rates in pts with Her2+ resectable EGA at the price of higher rates of diarrhea and leukopenia.

...Patients with HER2 3+ overexpression…at baseline demonstrated significantly better survival (P = .007) or treatment response (P = .016), respectively...Three-year progression-free and overall survival (OS) were 57% and 71%, respectively (median follow-up, 32.1 months)....Addition of trastuzumab and pertuzumab to nCRT in patients with HER2-positive EAC is feasible and demonstrates potentially promising activity compared with historical controls.