Long-term survival of a 50-year-old man with metastatic pancreatic cancer on a combination of nal-IRI + 5-FU/LV in 2nd line treatment − case study

Recommended treatment for advanced pancreatic cancer

Pancreatic cancer is often detected at an advanced stage, where curative treatment is no longer possible. In the 1st line of palliative treatment, FOLFIRINOX regimen or a doublet of gemcitabine + nab-paclitaxel is recommended. The GENERATE study, presented at the European Society for Clinical Oncology (ESMO) congress in 2023, showed that in the 1st line of palliative treatment, gemcitabine + nab-paclitaxel doublet offers greater benefit than FOLFIRINOX.

In the 2nd line of palliative treatment − upon progression of pancreatic cancer after gemcitabine-based therapy − pegylated liposomal irinotecan (nal-IRI) in combination with 5-fluorouracil (5-FU) and leucovorin (LV) is recommended. In the 2nd line, a regimen with continuous 5-FU (possibly in combination with oxaliplatin) can also be used for patients who were treated with a gemcitabine regimen in the 1st line, or gemcitabine monotherapy or in combination for patients treated with a 5-FU regimen in the 1st line.

Case description

Surgical procedure + adjuvant chemotherapy

In December 2020, a 48-year-old man was examined for painless jaundice. This father of 2 minor children had a history of allergic conjunctivitis, dyslipidemia, knee osteoarthritis, did not take any chronic medication, and did not smoke. Endoscopic ultrasonography revealed a 2 × 2 cm mass in the head of the pancreas, and a biopsy showed a suspected cytological finding. CA 19-9 level was 340 U/ml, and the patient reported a 13 kg weight loss over 4 months. Additional PET/CT examination showed no signs of generalization, and the patient was indicated for surgery.

In May 2021, a right duodenopancreatectomy with pylorus resection, lymphadenectomy, and cholecystectomy was performed. Histological examination revealed ductal adenocarcinoma of the pancreas 30 × 25 × 30 mm with invasion into the duodenum, ductus choledochus, retroperitoneum, perineural invasion, lymphangioinvasion, and angioinvasion. Resection margins were negative (R0), and 5 lymph node metastases were found (pT2 pN2 pMX).

Afterward, the patient underwent adjuvant chemotherapy with a modified FOLFIRINOX regimen (mFOLFIRINOX). From June to December 2021, he completed 12 series with a gradual reduction of oxaliplatin dose to 75% due to peripheral neuropathy. After treatment, the disease showed no relapse, PET/CT findings were negative, tumor markers were normal (CA 19-9 23.3 U/ml), and genetic testing showed no BRCA1/2 mutations or mutations in DNA repair mechanisms (MMR). The patient was further monitored in remission of the disease.

1st line of palliative treatment

In May 2022, an elevation of CA 19-9 to 949.4 U/ml was detected, and CT examination confirmed a relapse of the disease. Clinically, the patient showed no worsening, no weight loss, and had mild dyspeptic symptoms. From May to November 2022, he underwent 1st line palliative chemotherapy with gemcitabine + nab-paclitaxel over 7 cycles with dose reduction to 80% due to hematotoxicity and neurotoxicity.

During examination in September 2022, disease stabilization with a decrease in CA 19-9 to 172 U/ml was described, but by the end of 2022, a significant elevation of CA 19-9 to 2503 U/ml and disease progression on PET/CT (new lesion in the right liver lobe) were detected. The gemcitabine + nab-paclitaxel regimen was terminated.

2nd line palliative treatment

The patient was 50 years old at that time, clinically in excellent performance state (ECOG PS 0–1) with a very good quality of life. According to recommendations, after the failure of gemcitabine-based chemotherapy, a regimen with nal-IRI in combination with 5-FU/LV is appropriate, whose efficacy was confirmed in the NAPOLI-1 clinical trial, which led to an extension of median overall survival from 4.2 to 6.1 months compared to 5-FU/LV alone.

In January 2023, the patient began treatment with nal-IRI + 5-FU/LV regimen in the 2nd line of treatment. Initial CA 19-9 level was 4523 U/ml. Among side effects, grade 2 fatigue and grade 1–2 gastrointestinal toxicity (nausea and burning abdominal pain as an accentuation of chronic issues) were noted.

In May 2023, after the 7th cycle of treatment, partial remission with regression of the lesion in the right liver lobe and a significant decrease in CA 19-9 to 613 U/ml was detected. In August 2023 (after the 15th cycle of treatment), partial remission persisted, with a further decrease in CA 19-9 to 290 U/ml, and subjectively, the patient reported satisfactory tolerance of the treatment and good quality of life.

In November 2023, CA 19-9 increased to 566 U/ml; however, PET/CT in December 2023 showed a negative finding. For clinical benefit, continuing therapy was recommended.

In January 2024, the 24th cycle of nal-IRI + 5-FU/LV regimen was administered. The patient has ECOG PS 0–1, no weight loss, no deterioration, lives with his family in good quality of life, takes family vacations, and still works as a programmer.

Conclusion

This case study illustrates the benefit of nal-IRI + 5-FU/LV regimen for metastatic pancreatic cancer after previous treatment with a gemcitabine regimen. It is a recommended sequence in both Czech and international guidelines. The results of the GENERATE study, which showed a greater benefit of chemotherapy doublet nab-paclitaxel + gemcitabine compared to mFOLFIRINOX triplet in the 1st line of palliative therapy for pancreatic cancer, also support its use.

(zza)

Source: Klimčíková P. Long-term quality survival of a young man with metastatic pancreatic cancer pretreated with gemcitabine + nab-paclitaxel regimen on nal-IRI + 5-FU/LV combination. Onkologie 2024; 18 (1): 68−73, doi: 10.36290/xon.2024.014.

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