Gastroesophageal Cancer

Question 1

Perioperative Therapy

Answer 1

Chemoradiation
Paclitaxel + carboplatin (category 1)
Fluorouracil(Capecitabine) + oxaliplatin (category 1)

Perioperative Chemotherapy
Fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) (category 1)
Fluoropyrimidine and oxaliplatin

Postoperative Systemic Therapy
Nivolumab only after preoperative chemoradiation with R0
resection and residual disease (category 1)

Neoadjuvant or Perioperative Immunotherapy
MSI-H/dMMR tumors
Nivolumab and ipilimumab followed by nivolumab
Pembrolizumab
Tremelimumab and durvalumab for neoadjuvant therapy only

Question 2

First Line Systemic Therapy: Adenocarcinoma

Answer 2

HER2 overexpression positive:
(fluorouracil or capecitabine) + (oxaliplatin or cisplatin) +
trastuzumab +- pembrolizumab (if PDL-1 CPS > 1 per FDA acc app KEYNOTE 811)

HER2 overexpression negative:
(fluorouracil or capecitabine) + (oxaliplatin or cisplatin)
+- pembrolizumab (category 1 if PDL-1 CPS > 10)
or
(fluorouracil or capecitabine) + oxaliplatin only + nivolumab (category 1 if PDL-1 CPS> 5)

MSI-H/dMMR tumors (independent of PD-L1 status):
Pembrolizumab
Dostarlimab-gxly
Nivolumab + ipilimumab
(fluorouracil or capecitabine) + oxaliplatin + (nivolumab or pembrolizumab)

Question 3

First line Therapy: Squamous Cell Carcinoma

Answer 3

Same as Adeno except:

No HER2 expression ( no trastuzumab regimens)

Nivolumab regimens recommended without regard to PDL-1 status

(fluorouracil or capecitabine) + oxaliplatin OR cisplatin) + nivolumab

Pembrolizumab regimens still category 1 if PDL-1 CPS >10

Question 4

Second Line or Subsequent Therapy: Adenocarcinoma
Preferred (7)
Certain Circumstances (5)

Answer 4

Preferred Regimens:
Ramucirumab and paclitaxel (category 1 for EGJ adenocarcinoma; category 2A for esophageal adenocarcinoma)
Fam-trastuzumab deruxtecan-nxki for HER2 overexpression positive
Docetaxel (category 1)
Paclitaxel (category 1)
Irinotecan (category 1)
Fluorouracil + irinotecan
Trifluridine and tipiracil for third-line or subsequent therapy for EGJ adenocarcinoma (category 1)

Useful in Certain Circumstances:
Entrectinib or larotrectinib for NTRK gene fusion-positive
Pembrolizumabe or (Nivolumab + ipilimumab) or Dostarlimab-gxly for MSI-H/dMMR
Pembrolizumab for TMB high (≥10 mutations/megabase)
Dabrafenib + trametinib for BRAF V600E mutated tumors
Selpercatinib for RET gene fusion-positive

Question 5

Second Line or Subsequent Therapy: Squamous Cell Carcinoma
Preferred (6)
Certain Circumstances (5)

Answer 5

Preferred Regimens:
Nivolumab (category 1)
Pembrolizumab for tumors with PD-L1 expression levels by CPS of ≥10 (category 1)
Docetaxel (category 1)
Paclitaxel (category 1)
Irinotecan (category 1)
Fluorouracil and irinotecan

Useful in Certain Circumstances:
Entrectinib or larotrectinib for NTRK gene fusion-positive
Pembrolizumabe or (Nivolumab + ipilimumab) or Dostarlimab-gxly for MSI-H/dMMR
Pembrolizumab for TMB high (≥10 mutations/megabase)
Dabrafenib + trametinib for BRAF V600E mutated tumors
Selpercatinib for RET gene fusion-positive