Treatment discontinuation and re-initiation of anti-PD-(L)1 agents in metastatic cancers

Tikkanen, Antti; Iivanainen, Sanna; Koivunen, Jussi

doi:10.1007/s00432-020-03217-7

Cited by 8 publications

(6 citation statements)

References 31 publications

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“…More recently, in a study by Warner et al, only five (15%) of 34 patients responded to anti-PD-1 re-treatment [ 8 ]. Other reports included only 3–8 patients [ 2 , 9 , 12 , 21 , 29 , 30 ]. Overall, 47% ( n = 9) of our patients responded to re-treatment with anti–PD-1 therapy.…”

Section: Discussionmentioning

confidence: 99%

Immunotherapy Discontinuation in Metastatic Melanoma: Lessons from Real-Life Clinical Experience

Asher

Israeli-Weller

Ben‐Betzalel

et al. 2021

Cancers

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Background: Immunotherapy has revolutionized outcomes for melanoma patients, by significantly prolonging survival and probably even curing a fraction of metastatic patients. In daily practice, treatment for responding patients is often discontinued due to treatment-limiting toxicity, or electively, following a major tumor response. To date, the criteria for a safe stop and the optimal duration of treatment remain unclear. Patients and methods: This is a real-world single-site cohort of 106 advanced melanoma patients who were treated with immunotherapy and who discontinued treatments in the absence of disease progression. Here, we describe their long-term outcomes, and analyze the differential characteristics between patients who ultimately experienced progression and those who remained in unmaintained durable response. Results: Patients were treated with anti-PD-1 monotherapy (81%) or in combination with ipilimumab (19%) for a median of 15.2 m (range, 0.7–42.3 m). Upon discontinuation, 75.5% had achieved a complete response (CR). After a median follow-up of 20.8 m (range, 6–58) from discontinuation, 32% experienced disease progression. Median time to progression was 8.5 m (range, 1.5–37). Response to re-induction with anti-PD-1 was observed in 47%. On multivariate analysis, achieving a non-CR response, immunotherapy given in advanced line, and shorter treatment duration were significantly associated with lesser progression-free survival. Conclusions: This is one of the few reports on real-world melanoma patients who discontinued immunotherapy while responding to treatment. This study reveals the key factors to bear in mind when considering an elective treatment cessation. Specifically, patients with non-CR as best response and patients treated in an advanced-line setting should be treated for longer periods, and elective discontinuation should not take place prior to 18 m.

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Section: Discussionmentioning

confidence: 99%

Immunotherapy Discontinuation in Metastatic Melanoma: Lessons from Real-Life Clinical Experience

Asher

Israeli-Weller

Ben‐Betzalel

et al. 2021

Cancers

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“…An elective treatment discontinuation before progression of 10%-30% was reported in real-world analyses in other cancer types. [9][10][11] We observed favorable survival outcomes after drug discontinuation, especially in patients with CR. Although the follow-up data were immature, half of all patients and two-thirds of patients with CR were free from treatment and progression for more than 2 years.…”

Section: Discussionmentioning

confidence: 78%

“…The protocol and clinical setting of the trial can explain the difference in results versus our observations. An elective treatment discontinuation before progression of 10%–30% was reported in real‐world analyses in other cancer types 9–11 …”

Section: Discussionmentioning

confidence: 93%

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Discontinuation of pembrolizumab for advanced urothelial carcinoma without disease progression: Nationwide cohort study

et al. 2022

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Pembrolizumab, an anti‐programmed death 1 monoclonal antibody, has revolutionized the treatment of metastatic urothelial carcinoma. However, the optimal treatment duration for treatment responders has not been established. To address this, we retrospectively assess the treatment outcomes and duration of pembrolizumab for patients whose best response was complete response (CR) or partial response (PR) in a Japanese nationwide cohort of platinum‐refractory metastatic urothelial carcinoma. Of 203 patients whose best response was CR or PR, 83 patients discontinued pembrolizumab before progression. The median pembrolizumab treatment duration was 6.9 months. The 2‐year relapse‐free survival (RFS), treatment‐free survival, and OS rates after discontinuation were 49.0%, 57.4%, and 74.5%, respectively. CR, higher hemoglobin levels, and a better Eastern Cooperative Oncology Group performance status at the time of discontinuation were associated with significantly better RFS. Pembrolizumab was re‐administered to 12 patients. Pembrolizumab re‐challenge resulted in CR, PR, stable disease, and progressive disease in six, three, two, and one patient, respectively. Propensity score‐matched landmark analysis revealed no significant OS difference between patients who continued or discontinued pembrolizumab at 6, 12, and 18 months ( p = 0.91, 0.99, and 0.25, respectively). Our findings demonstrated that patients with objective responses had favorable survival outcomes and suggested that pembrolizumab could be discontinued safely in this population. This study should drive further efforts to optimize the treatment duration for pembrolizumab responders.

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“…However, there is no clear evidence on how long treatment should continue 16,17 . Other studies have reported that the drug was effective once it was discontinued and readministered when it recurred 18,19 . If the tumor completely disappears as in the present case, then it may be possible to administer pembrolizumab for a certain period, discontinue it, and if cancer recurs, re‐challenge it.…”

Section: Discussionmentioning

confidence: 81%

Complete response of squamous cell carcinoma of the lung following treatment with pembrolizumab in an elderly patient: A case report

et al. 2020

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Complete response of non-small cell lung cancer (NSCLC) with immune checkpoint inhibitor (ICI) monotherapy is rare. Here, we encountered an elderly patient who showed complete response of NSCLC following treatment with pembrolizumab. An 84-year-old man with a history of bloody sputum for several weeks visited a general physician. At that time, a chest X-ray revealed a tumor shadow in the left middle lung field, and the patient was referred to our hospital. Following transbronchial biopsy, he was diagnosed with squamous cell carcinoma of the lung. Expression of programmed death ligand 1 (PD-L1) in tumor cells was 80% or more by immunostaining. Based on the above, immunotherapy with pembrolizumab was performed as first-line therapy. The cancer cells completely disappeared at the end of the fifth cycle. There were no side effects during the therapeutic course. Treatment with pembrolizumab continued for two years and was then discontinued at the patient's request. Since then, no tumor recurrence has been detected for about one and a half years without treatment. There have been few reports of lung cancer disappearing after treatment with pembrolizumab. In conclusion, in elderly NSCLC patients with PD-L1 expression of 50% or more, pembrolizumab should be considered as first-line treatment with the treatment period, and mechanism suggested in this report.

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Treatment discontinuation and re-initiation of anti-PD-(L)1 agents in metastatic cancers

Cited by 8 publications

References 31 publications

Immunotherapy Discontinuation in Metastatic Melanoma: Lessons from Real-Life Clinical Experience

Immunotherapy Discontinuation in Metastatic Melanoma: Lessons from Real-Life Clinical Experience

Discontinuation of pembrolizumab for advanced urothelial carcinoma without disease progression: Nationwide cohort study

Complete response of squamous cell carcinoma of the lung following treatment with pembrolizumab in an elderly patient: A case report

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