Dual Checkpoint Blockade and EGFR Inhibition Produce a Rare Complete Response in MSS Duodenal Cancer
A man in his 70s with recurrent microsatellite-stable duodenal adenocarcinoma achieved a complete radiographic and metabolic remission after treatment with nivolumab, ipilimumab, and cetuximab, despite low tumor mutational burden and progression on prior systemic therapy. The case stands out because the tumor biology would ordinarily predict resistance to immune checkpoint blockade. Even with those unfavorable markers, the disease regressed within months and remained in remission for years after treatment ended.
The sequence matters. The cancer first escaped standard chemotherapy, then shrank after a regimen that combined PD-1 and CTLA-4 inhibition with EGFR blockade, suggesting a biologic interaction that may have amplified antitumor immunity beyond what any single drug could have achieved alone.
Recurrent Duodenal Adenocarcinoma After Standard Therapy
Screening uncovered the original tumor after a positive fecal occult blood test, and endoscopy identified a semi-circumferential destructive lesion in the second portion of the duodenum. Pathology showed poorly differentiated adenocarcinoma. The patient underwent laparoscopic Whipple surgery on January 9, 2019, and the postoperative stage was pT4N0, stage IIB.
He then received eight cycles of adjuvant FOLFOX from February through June 2019. Surveillance MRI in September 2020 revealed recurrence with seeding lesions in the left upper abdomen and right anterior abdominal wall, about 15 months after completion of adjuvant therapy. The disease later behaved like an aggressive peritoneal relapse, a pattern that can be difficult to control once metastatic spread has taken hold in small bowel adenocarcinoma.
First-line systemic therapy with FOLFIRI plus bevacizumab ran from October 2020 to November 2021. Imaging showed an initial decrease in the peritoneal nodules, but the best overall response remained stable disease. By November 2021, one peritoneal lesion had enlarged to 1.8 × 1.2 cm, and that change was read as progression.
Molecular Testing Left Little Room for Standard Targeted Choices
Because the recurrent lesions were not suitable for biopsy and the archived surgical specimen was unavailable for extra immunohistochemistry, plasma-based molecular profiling was used. FoundationOne Liquid CDx identified microsatellite-stable disease with a blood tumor mutational burden of 1 mutation/Mb. No reportable alterations appeared in KRAS, NRAS, BRAF, ERBB2, FGFR1–3, PIK3CA, POLE, POLD1, or NTRK1–3. The only reportable alteration was an ASXL1 frameshift mutation, which may have reflected clonal hematopoiesis rather than tumor biology.
In practical terms, the molecular profile offered no obvious target. MSS status and very low TMB usually predict poor benefit from checkpoint inhibition, while the absence of RAS and RAF alterations merely kept EGFR targeting on the table without making it clearly effective. Cetuximab plus FOLFIRI was therefore chosen at progression, but the lesion enlarged after three cycles.
The tumor was not supposed to respond this way.
Tumor Regression After Nivolumab, Ipilimumab, and Cetuximab
After progression on cetuximab plus FOLFIRI, the patient declined additional cytotoxic chemotherapy. An off-label regimen combining nivolumab, ipilimumab, and cetuximab was discussed, informed in part by emerging data in refractory MSS colorectal cancer. He elected to proceed after discussion of limited evidence and the potential for immune toxicity.
Treatment began in February 2022 with ipilimumab 50 mg, nivolumab 100 mg, and cetuximab 400 mg every 3 weeks. Ipilimumab was given for four cycles, while nivolumab plus cetuximab continued for a total of 17 cycles. Within 3 months, CT showed marked regression of the peritoneal lesion from 2.1 × 1.4 cm to 1.9 × 0.5 cm, and PET/CT still showed weak residual metabolic activity. By October 2022, CT documented a complete radiographic response. PET/CT in February 2023 confirmed a complete metabolic response.
This pattern is biologically plausible even in an MSS tumor when the immune system is pushed hard enough. CTLA-4 blockade can broaden T-cell priming, PD-1 blockade can restore exhausted effector activity, and EGFR inhibition may alter tumor-cell signaling while also influencing the immune microenvironment. In a tumor that had already failed chemotherapy, the triple combination may have shifted the balance enough to permit a deep and durable immune response, although a single case cannot separate the contribution of each agent.
Immune Toxicity Was Real but Manageable
The remission did not come without cost. Grade 1 pruritus developed in April 2022. In July 2022, grade 2 adrenal insufficiency was diagnosed, leading to one cycle of withheld immune checkpoint therapy while cetuximab continued alone; oral cortisone replacement was started, and nivolumab plus cetuximab later resumed. Grade 1 vitiligo appeared in April 2023 across the hands, upper extremities, and trunk. PET/CT also detected grade 1 pneumonitis, prompting a temporary hold of immunotherapy until recovery.
These toxicities matter because they mirror the immune activation that likely drove the tumor response. Endocrine injury, cutaneous depigmentation, and pneumonitis are all familiar immune-related adverse events, and here they were manageable rather than treatment-ending. The case shows both sides of potent immune manipulation: disease control on one hand, clinically meaningful autoimmunity on the other.
A Durable Remission Extending Beyond Treatment
Nivolumab stopped in October 2023, and cetuximab continued as maintenance until January 2024, when financial constraints ended all anticancer therapy. At the latest follow-up in April 2026, the patient remained in complete remission, about 42 months after the first documented radiographic complete response and 27 months after stopping all anticancer treatment.
Long off-treatment remission is what makes this case unusual. In metastatic MSS duodenal adenocarcinoma, sustained complete responses are rarely seen, and durable control after therapy withdrawal is even less expected. The disease biology here appears to have crossed a threshold from refractory progression to stable immune-mediated suppression, and that shift persisted long after active treatment ended.
Why This Case Matters for MSS Small Bowel Adenocarcinoma
Small bowel adenocarcinoma remains a rare gastrointestinal cancer, and duodenal primaries are the most common site. Treatment strategies often borrow from colorectal cancer because prospective data are sparse. Yet this case argues that MSS small bowel adenocarcinoma may not be uniformly immunotherapy-resistant, especially when checkpoint blockade is combined with EGFR inhibition.
The finding should be interpreted cautiously. A single patient cannot establish synergy, define predictive biomarkers, or justify routine use of this regimen in MSS disease. The durable response does, however, create a concrete hypothesis for future trials: some MSS SBA tumors may remain immunologically vulnerable when multiple immune pathways are blocked together and tumor signaling is simultaneously targeted.
The unanswered question is not whether this patient responded. He clearly did. The real question is which biologic features made that response possible and whether any subset of MSS duodenal adenocarcinoma can be identified before treatment begins.