Gastrointestinal malignancies in pregnancy: practical considerations
Clare Anderson
, Al B. Benson III
Keywords: Maternal oncology treatment; gastrointestinal malignancies; chemotherapy during pregnancies
Submitted Feb 13, 2026. Accepted for publication Mar 12, 2026. Published online Apr 28, 2026.
doi: 10.21037/jgo-2026-1-0163
The diagnosis of gastrointestinal malignancy during pregnancy has traditionally been viewed as a rare clinical occurrence. However, converging demographic trends, including the rising incidence of gastrointestinal cancers among younger adults and the increasing age at first pregnancy, are making such scenarios more relevant to contemporary oncology practice. As these trends intersect, clinicians are more frequently confronted with situations in which oncologic urgency, fetal safety, and patient preferences must be balanced. This often occurs in the absence of high-level evidence (1). In this setting, pregnancy introduces a degree of complexity that challenges standard, algorithm-driven approaches to cancer care and necessitates individualized, gestational-age-specific decision-making (2,3).
In their case report, Eijsink and colleagues describe the multidisciplinary management of metastatic gastric cancer diagnosed during the third trimester of pregnancy. While the clinical course itself is notable, the broader relevance of this report lies in how treatment decisions were pragmatically adapted throughout pregnancy without compromising oncologic intent. In this case, close coordination among oncology, obstetrics, pharmacy, and critical care teams enabled timely adjustments in therapy as maternal and fetal considerations evolved. Ongoing shared decision-making with the patient and her partner further illustrates a practical framework for navigating competing priorities when standard treatment paradigms provide limited guidance.
From a clinical perspective, management of gastrointestinal cancers during pregnancy is inherently trimester-dependent. During the first trimester, concerns regarding teratogenicity and pregnancy loss frequently limit systemic treatment options, often shifting the balance toward treatment delay or consideration of pregnancy termination depending on disease aggressiveness and patient values. In contrast, during the second and third trimesters, decision-making increasingly focuses on balancing maternal disease control against risks of prematurity, fetal growth restriction, and neonatal complications (3-5). As illustrated in this case, these considerations are not static; rather, they evolve with gestational age, maternal clinical status, and response to therapy. Accordingly, reassessment over time, rather than dependence on a single treatment decision, is central to optimal care.
Within this trimester-specific framework, the authors’ decision to initiate fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy while deferring immunotherapy until the postpartum period is particularly instructive. Despite biomarker features that would ordinarily support the addition of immune checkpoint inhibition, the multidisciplinary team appropriately prioritized fetal safety in light of limited preclinical and clinical data regarding the use of programmed cell death protein 1 (PD-1) blockade during pregnancy (6,7). This approach embodies an common clinical reality in gastrointestinal oncology, namely that guideline-supported therapies may require modification when applied to special populations, and that restraint may represent sound clinical judgment rather than therapeutic compromise. Such decisions are best made through transparent discussions with patients, with explicit acknowledgment of both the known benefits of therapy and the uncertainties surrounding fetal risk.
The incorporation of therapeutic drug monitoring further highlights the practical contributions of this report, particularly in the context of physiologic changes associated with pregnancy. Although pharmacokinetic data from a single patient cannot redefine standard practice, existing literature suggests that commonly used gastrointestinal agents, including fluoropyrimidines and platinum compounds, may be administered during later trimesters without substantial alterations in drug disposition (4,5). In this context, pharmacokinetic assessment serves as a supportive adjunct to clinical judgment, enabling safe delivery of established regimens rather than prompting deviation from standard dosing strategies. To contextualize these decisions more broadly, commonly used systemic therapies for gastrointestinal malignancies and their reported use during the second and third trimesters of pregnancy are summarized in Table 1. This overview is intended to support clinical discussion rather than prescribe management, emphasizing that available data are largely derived from retrospective series, case reports, and extrapolation from non-gastrointestinal malignancies (4,7,8).
Table 1
| Drug/class | Common GI cancer indications | Use in pregnancy (2nd/3rd trimester) |
|---|---|---|
| 5-FU | Colorectal, gastric, esophageal | Used with caution; acceptable fetal outcomes reported |
| Capecitabine | Colorectal, gastric | Generally avoided; limited safety data, unpredictable PK |
| Oxaliplatin | Colorectal, gastric | Used with caution; acceptable outcomes reported |
| Cisplatin | Gastric, esophageal | Used with caution; risk of IUGR, preterm birth |
| Irinotecan | Colorectal | Used selectively; risk of preterm birth, neonatal cytopenias |
| Gemcitabine | Pancreatic, biliary, gastric | Used with caution; risk of IUGR, preterm birth |
| Trastuzumab | HER2-positive gastric, esophageal | Contraindicated (oligohydramnios, fetal renal toxicity) |
| Methotrexate | Rarely used in GI cancers | Contraindicated (known teratogenicity) |
| Paclitaxel | Gastric, esophageal | Used with caution; acceptable fetal outcomes reported |
| Docetaxel | Gastric, esophageal | Used with caution; limited reports, generally favorable |
| Carboplatin | Gastric, esophageal, pancreatic | Used with caution; risk of preterm birth, low birth weight |
| Bevacizumab† | Colorectal | Contraindicated (anti-angiogenic mechanism; embryo-fetal toxicity) |
| Ramucirumab† | Gastric, colorectal | Contraindicated (theoretical embryo-fetal toxicity) |
| Pembrolizumab* | MSI-H/dMMR GI cancers | Use with extreme caution; risk of preterm birth, neonatal irAEs |
| Nivolumab* | MSI-H/dMMR GI cancers | Use with extreme caution; risk of preterm birth, IUGR |
| Encorafenib§ | BRAF V600E-mutated colorectal cancer | Generally avoided; no pregnancy safety data, potential embryo-fetal toxicity |
| Leucovorin | Colorectal (with 5-FU) | Limited data; use only if clinically indicated |
Table reflects reported experience primarily in the second and third trimesters. Use of systemic therapy during the first trimester is generally avoided due to teratogenic risk. Data are derived largely from retrospective series, case reports, and extrapolation from non-gastrointestinal malignancies. †, anti-angiogenic and targeted therapies: other targeted agents used in gastrointestinal cancers include cabozantinib, sorafenib, regorafenib, lenvatinib, fruquintinib, and zolbetuximab. These agents are generally avoided during pregnancy due to limited human data and concerns for embryo-fetal toxicity, particularly related to angiogenesis inhibition and developmental signaling pathways. ‡, other cytotoxic agents: Trifluridine/tipiracil is used in later-line colorectal cancer but lacks pregnancy-specific safety data and is generally avoided during pregnancy. §, molecularly targeted therapies: targeted therapies for specific molecular subsets include other BRAF-directed agents (dabrafenib, trametinib) and KRAS G12C inhibitors (adagrasib, sotorasib). Pregnancy-specific safety data for these agents are lacking, and they are generally avoided during pregnancy outside of exceptional circumstances. *, immune checkpoint inhibitors: other immune checkpoint inhibitors used in gastrointestinal malignancies include dostarlimab, tremelimumab, durvalumab, tislelizumab, atezolizumab, and retifanlimab. Data regarding use during pregnancy are extremely limited. Based on their mechanism of action and available preclinical and case-based evidence, immune checkpoint inhibitors are generally avoided during pregnancy due to concerns regarding fetal immune dysregulation, preterm birth, and intrauterine growth restriction. 5-FU, 5-fluorouracil; BRAF, B-Raf proto-oncogene, serine/threonine kinase; dMMR, deficient mismatch repair GI, gastrointestinal; HER2, human epidermal growth factor receptor 2; irAEs, immune-related adverse events; IUGR, intrauterine growth restriction; MSI-H, microsatellite instability-high; PK, pharmacokinetics.
Importantly, this case also highlights the central role of shared decision-making in the care of pregnant patients with gastrointestinal cancers. When evidence is limited and risks cannot be fully quantified, aligning treatment decisions with patient values becomes essential. Decisions regarding treatment initiation, sequencing, and timing of delivery must reflect not only clinical feasibility but also patient priorities, which may shift as pregnancy progresses (2,3).
As the incidence of gastrointestinal cancers among reproductive-aged patients continues to rise, there is an increasing need for practical frameworks to guide care during pregnancy. Multidisciplinary collaboration, trimester-specific risk assessment, and shared decision-making should form the foundation of management. Beyond individual cases, collaborative registries and longitudinal outcome data will be critical to better define maternal and neonatal outcomes and to inform future guidance (2,3). Until such data are available, reports such as this provide valuable insight into how thoughtful, patient-centered care can be delivered when evidence is limited and clinical stakes are high.
Acknowledgments
None.
Footnote
Provenance and Peer Review: This article was commissioned by the editorial office, Journal of Gastrointestinal Oncology. The article did not undergo external peer review.
Funding: None.
Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-1-0163/coif). A.B.B. reports serving as a scientific advisor or consultant for multiple pharmaceutical and biotechnology companies, including Bristol Myers Squibb, AbbVie, Janssen Oncology, Apexigen, Artemida Pharma, Xencor, Mirati Therapeutics, Boston Scientific, GlaxoSmithKline, Astellas Pharma, Boehringer Ingelheim, Merck, Jazz Pharmaceuticals, Pfizer, Amgen, Takeda, Novartis, Taiho Pharmaceutical, Incyte, and others. He has also participated in multiple Data Monitoring Committees (DMCs) for industry-sponsored trials and reports institutional or advisory relationships with organizations including Teladoc, Lewin Group, DRG, The Nucleus Group, and White Swan. In addition, A.B.B. reports leadership or advisory roles with ECOG-ACRIN, the NCCN and NCCN Foundation boards, the Patient Advocate Foundation and National Patient Advocate Foundation, and the advocacy organization Fight Colorectal Cancer. Travel support for professional meetings (including NCCN and ACCC) is reported. The other author has no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
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