TREMFYA - Use in Adult Patients with Plaque Psoriasis or Psoriatic Arthritis with a History of Malignancy

SUMMARY

• The company cannot recommend any practices, procedures, or usage that deviates from the approved labeling.
• In moderate to severe plaque psoriasis (PsO), a patient was excluded from participating in VOYAGE 1 and VOYAGE 2 if he/she currently had a malignancy or a history of malignancy except nonmelanoma skin cancer (NMSC) within 5 years.^1,2
• In a descriptive analysis of safety data from VOYAGE 1 and VOYAGE 2, malignancy events were reported among 18 patients with PsO who had a baseline history of malignancy (excluding NMSC) over a period of 5 years.^3,4
• Two serious adverse events (SAEs) of malignancies (excluding NMSC) were reported among 19 patients with a history of malignancy (excluding NMSC) through 3 years of continuous treatment with TREMFYA in VOYAGE 1 and VOYAGE 2.⁵
• In active psoriatic arthritis (PsA), a patient was excluded from participating in DISCOVER 1 and DISCOVER 2 if he/she currently had a malignancy or a history of malignancy within 5 years before screening (with the exception of an NMSC that had been adequately treated with no evidence of recurrence for at least 3 months before the first study drug administration or cervical carcinoma in situ that had been treated with no evidence of recurrence for at least 3 months before first study drug administration).^6,7
• Four retrospective studies assessed the effectiveness and safety of TREMFYA in patients with moderate to severe PsO with a history of malignancy.^8-11
• A case series and 2 case reports, which described the use of TREMFYA in patients with PsO and a history of malignancy, are summarized below.^12-14

CLINICAL DATA IN moderate to severe PLAQUE PSOriasis

Phase 3 Studies

Blauvelt et al (2023)³ conducted a descriptive analysis of the safety of TREMFYA in patients with PsO with a history of malignancy (excluding NMSC). The study evaluated malignancy events in VOYAGE 1 and VOYAGE 2 through 5 years.

• History of malignancy at baseline was reported in 18 of 1721 patients treated with TREMFYA.
• Compared with the total TREMFYA-treated VOYAGE population, patients with prior malignancy were older (mean age, 60.8 vs 43.5 years), had longer PsO duration (mean, 23.6 vs 17.8 years), and had shorter TREMFYA exposure (median, 4.3 vs 4.7 years).
• Of the 18 patients with prior malignancy, 15 (83%) patients achieved a final Psoriasis Area and Severity Index (PASI) of <1. One patient discontinued TREMFYA after 20 weeks of exposure due to lack of efficacy (baseline PASI score: 16.4; last visit PASI score: 7.0). See Table: Demographics and Outcomes in Patients with PsO with a History of Malignancy from VOYAGE 1 and VOYAGE 2.

Blauvelt et al (2019)⁵ reported the occurrence of SAEs of malignancies (excluding NMSC) through 3 years of continuous TREMFYA treatment in patients with a history of malignancy (excluding NMSC) during the VOYAGE 1 and VOYAGE 2 studies.

• Of the 1826 patients in VOYAGE 1 and VOYAGE 2, 19 (1.0%) patients had a history of malignancy (excluding NMSC) at baseline (TREMFYA, n=10; placebo, n=4; adalimumab, n=5).
• Prior malignancies included kidney, prostate, lung, testicular, thyroid, cervical, rectal, colon, and breast cancers, melanoma, and dermatofibrosarcoma.
• SAEs of malignancies (excluding NMSC) were reported in 2 of the 19 patients.
  • A 76-year-old patient with a history of prostate cancer (2007) who was treated with TREMFYA developed metastatic invasive papillary breast carcinoma on study day 202 of VOYAGE 1 and withdrew from the study. The patient recovered from this SAE.
  • A 57-year-old patient with a history of squamous cell bronchial carcinoma (1997 to 2007) who was treated with adalimumab and crossed over to open-label TREMFYA during VOYAGE 2 had a recurrence with metastases at study day 753 and died.

real-world evidence

Retrospective Studies

Mortato et al (2025)⁸ conducted a retrospective multicenter study (EARLY study) to assess the clinical outcomes and safety of TREMFYA in patients with moderate to severe plaque PsO with chronic infections, malignancies, or heart disease.

• Of the 1024 patients enrolled in the study, 65 (6.3%) patients had cancer, with 51 (78%) patients classified in the precedent cancer (PC) group (diagnosed before initiating treatment with TREMFYA) and 14 (22%) patients in the intercurrent cancer (IC) group (diagnosed during treatment with TREMFYA).
• The mean (standard deviation [SD]) time from cancer diagnosis to initiating TREMFYA ranged from 34.6 (43.5) months for hematological cancer to 89.6 (57.0) months for gastrointestinal tract cancers.
• The mean (SD) follow-up duration for patients receiving TREMFYA after cancer diagnosis ranged from:
  • PC group: 95.2 (70.9) weeks for breast cancer to 164.7 (79.1) weeks for melanoma
  • IC group: 26.0 weeks for “other tumors” (n=1) to 150.0 (66.4) weeks for genitourinary system tumors
• In the PC group, genitourinary system tumors were most common (n=15), followed by breast (n=9), gastrointestinal (n=8), melanoma (n=7), other tumors (n=5), hematological cancers (n=4), and lung cancer (n=3).
• In the IC group, genitourinary tumors and lung cancer were equally frequent (n=4 each), followed by hematological cancers (n=2), and breast, gastrointestinal, melanoma, and other tumors (n=1 each).
• Three patients (lung cancer, n=2; non-Hodgkin lymphoma [NHL], n=1) discontinued TREMFYA immediately after cancer diagnosis.
• Based on cancer risk, patients were stratified into low-risk group (NMSC and nonrecurrence >5 years) and high-risk group (active cancers and recently diagnosed).
• The mean (SD) time from cancer diagnosis to initiating TREMFYA was:
  • High-risk group: 11.8 (15.5) months
  • Low-risk group: 113.3 (58.5) months
• The mean (SD) follow-up duration for patients receiving TREMFYA was:
  • High-risk group: 116.3 (76.6) weeks
  • Low-risk group: 119.3 (76.3) weeks
• No new cancer recurrences or progression were observed.

Ramos et al (2025)¹¹ conducted a retrospective multicenter study for over 52 weeks to evaluate the efficacy and safety of TREMFYA in patients with moderate to severe PsO and a history of malignancy.

• Adults treated with subcutaneous (SC) TREMFYA 100 mg for ≥24 weeks with a diagnosis of neoplasm in the last 10 years were included.
• The primary endpoint was to evaluate cancer recurrence, progression, or emergence of new malignancies. Secondary endpoints included PASI, body surface area (BSA), and Dermatology Life Quality Index (DLQI) at baseline and weeks 16, 24, and 52.
• Of the 30 patients included, 73.3% had a history of malignancy within the past 5 years.
  • Cutaneous melanoma was the most frequently reported cancer (24.1%), followed by bladder, breast, lung, and cervical cancers (10.3% each).
• Baseline characteristics of the study population are presented in Table: Select Baseline Characteristics.

• The mean (SD) PASI score at weeks 16, 24, and 52 was 0.8 (1.7), 0.5 (1.8), and 0.2 (0.6), respectively (P<0.0001 vs baseline). The mean (SD) BSA involvement and DLQI score at week 52 was 0.5% (1.3; P<0.0001 vs baseline) and 0.9 (2.6; P=0.003 vs baseline), respectively.
• No tumor progression was observed among patients with active malignancies (n=11) during the 52-week follow-up. One patient with stage IV melanoma died from brain metastases. For more details, see Table: Clinical Course and Oncologic Outcomes in Patients with Active Malignancy through Week 52.
• No recurrence was observed during treatment with TREMFYA in patients with a history of malignancy (n=19).

• Two different patients were diagnosed with new malignancies during TREMFYA treatment: endometrial adenocarcinoma at 6 months in 1 patient and melanoma in situ after 2 years in another patient. In both patients, TREMFYA was continued, with no tumor progression or PsO worsening observed during follow-up.
• Before TREMFYA initiation, 1 case each of urothelial bladder carcinoma and prostate cancer was diagnosed during ixekizumab (after 2 years) and ustekinumab (after 1 year) treatment, respectively.
• No SAEs or drug-related treatment discontinuations were reported during the follow-up period.

Gracia Cazaña et al (2024)⁹ conducted a retrospective multicenter study to assess the safety and efficacy of TREMFYA in patients with moderate to severe PsO and a history of malignancy.

• Patients >18 years of age treated with TREMFYA with a diagnosis of neoplasm in the last ≤5 years were included (n=20), and patients with <12 weeks of follow-up period were excluded.
• Of the 20 patients enrolled in the study, 14 patients had active cancers, with an average time from cancer diagnosis of 3.6 years.
• The mean follow-up time was 36 weeks, and the maximum and median follow-up periods were both 52 weeks.
• All patients were previously treated with systemic and biologic therapies, including adalimumab (n=10), etanercept (n=9), and apremilast (n=9).
  • Prior to switching to TREMFYA, the majority of patients were previously treated with apremilast (n=10) and ustekinumab (n=6).
• Most malignancies were solid tumors, including head and neck cancer (n=3), melanoma (n=2), and endometrial cancer (n=2). Other tumor types were vulvar (n=1), breast (n=2), cervical (n=1), colon (n=1), prostate (n=5), chronic lymphocytic leukemia (n=1), Kaposi sarcoma (n=1), and larynx (n=1).
• The percentage of patients who achieved PASI ≤3 at weeks 12 and 52 was 80% and 87.5%, respectively; 68.8% of patients achieved PASI ≤1.
• Clinical outcomes including mean PASI, BSA, DLQI, and pruritus visual analog scale (VAS) scores from baseline to week 52 are presented in Table: Clinical Outcomes from Baseline to Week 52.

• At the end of the study, a 52-week survival rate of 100% (n=20) was observed, including patients with concomitant active cancers (n=14).
• No adverse events (AEs), SAEs, or discontinuations related to the TREMFYA safety profile were reported in patients with or without active cancer.

Al-Rabai et al (2023)¹⁰ conducted a 60-week retrospective study to assess the real-world effectiveness and safety of TREMFYA in adults with moderate to severe plaque PsO, including patients with a history of malignancy.

• A total of 104 patients were included in this study.
• Six patients had a history of malignancy, including cutaneous melanoma, bladder cancer, colon cancer, papillary thyroid carcinoma, breast cancer, and NHL.
• All patients were in remission and had a cancer diagnosis ≥4 years prior to initiating TREMFYA treatment.
• No recurrence of cancer was observed in any of the 6 patients during the 60-week follow-up period.

Case Series/Case Reports

Mastorino et al (2022)¹² evaluated safety and effectiveness of TREMFYA in patients with moderate to severe PsO and a prior history of cancer.

• Of 75 patients treated with TREMFYA, 7 had a prior history of malignancy, including NMSC (basal cell carcinoma/squamous cell carcinoma [n=3]), melanoma (n=1), leiomyosarcoma (n=1), clear cell renal carcinoma (n=1), and ductal breast cancer (n=1).
• Two of 7 patients had received prior biologics (etanercept and adalimumab, n=1; ustekinumab, n=1).
• All patients were treated with TREMFYA for at least 11 months, with regular ongoing follow-up.
• PASI >70 was achieved in 6 patients. One patient discontinued treatment after 1 year due to intolerance.
• All patients experienced low-grade neoplasia, however possible concern of cancer recurrence was not observed with TREMFYA.

Ke et al (2025)¹⁴ reported a case of a 61-year-old man with pulmonary metastases following colon cancer resection and a 10-year history of PsO, which had worsened during sintilimab treatment and was subsequently managed with TREMFYA.

• The patient received combination therapy with oxaliplatin, calcium folinate, and 5-fluorouracil (5-FU) on day 1, along with a continuous infusion of 5-FU over 46 hours. In addition, sintilimab was administered as immune checkpoint blockade, and bevacizumab was administered as antiangiogenic therapy on day 1. This regimen was administered every 3 weeks as 1 cycle.
• The patient had a prior history of mild plaque PsO that was well controlled with topical corticosteroids. Following initiation of immune checkpoint therapy, the patient developed extensive PsO‑like cutaneous lesions. Given the severity of the skin involvement and its temporal association with the programmed cell death receptor (PD)-1 inhibitor sintilimab (known to activate PsO‑associated immune pathways, including Th17 cells), a diagnosis of PD-1 inhibitor-exacerbated PsO was made.
• Sintilimab was temporarily discontinued and was subsequently reintroduced to maintain the efficacy of anticancer therapy.
• Subsequently, TREMFYA 100 mg SC every 4 weeks was initiated, followed by maintenance therapy every 8 weeks. Following the second dose of TREMFYA, the PASI score decreased from 21.2 at baseline to 7.2 (66% improvement), with a marked reduction observed in the number of lesions. At week 25, a PASI score of 2 was achieved (90% improvement from baseline).
  • Large deep-red plaques with thick scaling at baseline faded to faint red with fine scaling after the second dose and further improved to light red with minimal residual scaling and resolution of elevation at week 25.
• No signs of infections, no reactivation of latent infections, and no adverse drug reactions were reported during the treatment period.
• Despite continuation of the prior chemotherapy regimen, chest computed tomography (CT) revealed a slight reduction in the size of pulmonary nodules after 10 weeks of TREMFYA therapy compared with baseline imaging; the pulmonary nodules remained stable at week 29.

Kamiya et al (2020)¹³ reported a case of a 58-year-old male patient with non-small cell lung cancer and plaque PsO treated with carboplatin (CBDCA) plus nanoparticle albumin-bound paclitaxel (nab-PTX) therapy and TREMFYA.

• The patient received cyclosporine 150-300 mg/day for 6 years with well-controlled skin lesions. However, the patient was subsequently administered ustekinumab due to deterioration in renal function.
• Twenty-five months after treatment with ustekinumab, CT showed a nodular lesion in the left upper lobe, indicating lung cancer. Ustekinumab was then replaced with apremilast.
• After 2 months, apremilast was discontinued due to worsening skin lesions and TREMFYA was then initiated.
• Three months after the administration of TREMFYA, a diagnosis of lung adenocarcinoma was made from histopathological findings of transbronchial lung biopsy, leading to temporary discontinuation of TREMFYA.
• The patient was started with CBDCA plus nab-PTX for advanced non-small cell lung cancer (cT2aN3M0, stage IIIB).
• The nodular lung cancer lesion showed very good partial response after treatment with 4 courses of CBDCA plus nab-PTX.
• The skin lesions deteriorated during treatment with CBDCA plus nab-PTX and ameliorated after the readministration of TREMFYA.
• Further deterioration of skin lesions was not observed, and no lung cancer relapse was observed for over 3 months.

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 15 April 2026.