Reported by Prof Eric Van Cutsem, UZ Leuven
The KEYNOTE-585 and MATTERHORN studies delve into the role of adjuvant and neoadjuvant treatment involving checkpoint inhibitors in gastric cancer. Both trials randomise patients into groups undergoing chemotherapy before and after surgery, either with a placebo or a checkpoint inhibitor. In KEYNOTE-585, pembrolizumab was used as the checkpoint inhibitor, whereas the MATTERHORN study utilised durvalumab.
Comparisons between the trials reveal similarities and disparities in their designs, with intriguing outcomes. Notably, patients receiving checkpoint inhibition in both studies exhibited superior pathological complete response and pathological staging. While results for event-free survival and overall survival are pending, KEYNOTE-585 demonstrates a positive trend. Although statistical significance was not achieved with pembrolizumab for the overall study population, certain subgroups seem to benefit from the treatment.
The KEYNOTE-811 study explores treatment options for HER2+ metastatic gastric/gastroesophageal junction cancer, combining trastuzumab and chemotherapy with or without pembrolizumab. Early findings indicated significant improvements in objective response rate. At ESMO2023, PFS results were presented, revealing substantial benefits, especially in tumours with dual HER2+ and PD-L1 overexpression. Based on these findings, EMA recommends the combination of pembrolizumab with trastuzumab and chemotherapy as the first-line treatment for these patients.
The GENERATE study, focusing on first-line metastatic pancreatic cancer, yielded inconclusive outcomes. The study randomised patients into three groups: classic Nab-PTX with gemcitabine, mFOLFIRINOX, or S-IROX regimens. Despite expectations favouring the triplet therapy, Nab-PTX with gemcitabine exhibited superior outcomes, leading to a better median overall survival. Consequently, the doublet combination therapy is advised as the primary treatment. However, triplet therapy remains an option, especially for patients in good condition, as suggested by the NAPOLI study, for those with metastatic pancreatic adenocarcinoma.
In the PREOPANK-2 study, researchers compared FOLFIRINOX and gemcitabine-based chemoradiotherapy for (borderline) resectable pancreatic cancers. Prior trials favoured neoadjuvant gem-based radiotherapy over upfront surgery. In this study, FOLFIRINOX and gem-based radiotherapy were compared before surgery. Expectations leaned toward FOLFIRINOX, but the OS results were comparable between the treatment arms. A drawback in this study was the requirement for patients to undergo eight cycles of FOLFIRINOX before surgery, leading to numerous discontinuations. This may be attributed to the original FOLFIRINOX regimen, resulting in low dose intensity due to patient toxicity-related discontinuations.
References:
Kohei Shitara – Pembrolizumab plus chemotherapy vs chemotherapy as neoadjuvant and adjuvant therapy in locally-advanced gastric and gastroesophageal junction cancer: The Phase 3 KEYNOTE-585 study. ESMO23 – LBA74
Salah-Eddin Al-Batran – Pathological complete response (pCR) to durvalumab plus 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) in resectable gastric and gastroesophageal junction cancer (GC/GEJC): interim results of the global, Phase 3 MATTERHORN study. ESMO23 – LBA73
Yelena Y. Janjigian – Pembrolizumab plus Trastuzumab and Chemotherapy for HER2+ Metastatic Gastric or Gastroesophageal Junction (mG/GEJ) Adenocarcinoma: Survival results from the Phase 3, Randomized, Double-blind, Placebo-controlled KEYNOTE-811 Study. ESMO23 – 1511O
Akhira Ohba – Nab-paclitaxel plus gemcitabine versus modified FOLFIRINOX or S-IROX in metastatic or recurrent pancreatic cancer (JCOG1611, GENERATE): a multicenter, randomized, open-label, three-arm, phase 2/3 trial. ESMO23 -1616O
Bas Groot Koerkamp – Neoadjuvant chemotherapy with FOLFIRINOX versus neoadjuvant gemcitabine-based chemoradiotherapy for borderline resectable and resectable pancreatic cancer (PREOPANC-2): a multicenter randomized controlled trial. ESMO23 – LBA83
With the educational support of:
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