Continuous Versus 1-Year Fixed-Duration Nivolumab in Previously Treated Advanced Non–Small-Cell Lung Cancer: CheckMate 153

Waterhouse, David; Garon, Edward B.; Chandler, Jason C.; McCleod, Michael; Hussein, Maen; Jotte, Robert M.; Horn, Leora; Daniel, Davey B.; Keogh, George P.; Creelan, Ben; Einhorn, Lawrence H.; Baker, Justin; Kasbari, Samer S.; Nikolinakos, Petros; Babu, Sunil; Couture, Félix; Leighl, Natasha B.; Reynolds, Craig H.; Blumenschein, George R.; Gunuganti, Vijay; Li, Ang; Aanur, Nivedita; Spigel, David R.

doi:10.1200/jco.20.00131

Cited by 143 publications

(116 citation statements)

References 16 publications

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“…Although a prospective study indicated that treatment discontinuation was associated with detrimental survival in NSCLC, 3 CMR by FDG-PET selects a patient population with favorable response to treatment. In the presented cohort of patients, 15 of 27 (56%) patients with CMR have paused immunotherapy following FDG-PET, none of them has progressed.…”

Section: Discussionmentioning

confidence: 99%

“…However, recently published results from CheckMate-153 demonstrated inferior survival rates in patients ceasing immunotherapy after 1 year, 3 therefore, optimal treatment duration of immunotherapy in advanced NSCLC remains unknown. Protocols from published phase-III trials implemented treatment for a period of approximately 24 months or until evidence of disease progression or unbearable toxicity.…”

Section: Introductionmentioning

confidence: 99%

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Complete metabolic response in patients with advanced non-small cell lung cancer with prolonged response to immune checkpoint inhibitor therapy

Ferdinandus

Metzenmacher

Kessler

et al. 2021

J Immunother Cancer

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IntroductionImmunotherapy is the new standard of care in advanced nonsmall cell lung cancer (NSCLC). Recently published data show that treatment discontinuation after 12 months of nivolumab treatment is associated with shorter survival. Therefore, the ideal duration of immunotherapy remains unclear, and finding markers of beneficial outcomes is of great importance. Here, we determine the proportion of complete metabolic responses (CMR) in patients who have not progressed after 24 months of immunotherapy.MethodsThis is a retrospective analysis of 45 patients with positron emission tomography using 2-[18F]fluoro-2-deoxy-D-glucose imaging for assessment of residual metabolic activity after at least 24 months. CMR was defined as uptake in tumor lesions below background levels, using mediastinum as a reference. ResultsOut of 45 patients, 29 patients had a CMR (64%). CMR was observed more frequently in non-first-line patients. Patients with CMR were younger (median 65.7 vs 75.5, p=0.03). Fourteen patients with CMR have discontinued therapy and have not progressed until time of analysis; however, median follow-up was only 5.6 (range 0.8–17.0) months.ConclusionAfter a minimum of 24 months of palliative immunotherapy for NSCLC, CMR occurred in almost two thirds of patients. Potentially, achievement of CMR might identify patients, for whom palliative immunotherapy may be safely discontinued.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Complete metabolic response in patients with advanced non-small cell lung cancer with prolonged response to immune checkpoint inhibitor therapy

Ferdinandus

Metzenmacher

Kessler

et al. 2021

J Immunother Cancer

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“…16 In the intent-totreat population, continuous nivolumab was associated with longer median OS compared with 1-year fixedduration treatment (not reached vs 28.8 months; HR, 0.62 (95% CI, 0.42 to 0.92)). 16 We conducted a multivariable analysis of baseline demographics and clinical variables to evaluate their association with progression. The results indicate that younger age, history of brain metastasis, and a higher post-PD-1 LDH were associated with earlier time to progression.…”

Section: Discussionmentioning

confidence: 88%

“… 15 In a recent exploratory analysis of CheckMate 153, which evaluated continuous versus 1-year fixed-duration nivolumab in previously treated advanced non-small cell lung cancer patients, continuing nivolumab beyond 1 year appeared to be associated with improved outcomes. 16 In the intent-to-treat population, continuous nivolumab was associated with longer median OS compared with 1-year fixed-duration treatment (not reached vs 28.8 months; HR, 0.62 (95% CI, 0.42 to 0.92)). 16 …”

Section: Discussionmentioning

confidence: 89%

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Real-world experience with elective discontinuation of PD-1 inhibitors at 1 year in patients with metastatic melanoma

Pokorny

McPherson

Haaland

et al. 2021

J Immunother Cancer

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BackgroundRandomized trials evaluating programmed cell death protein 1 (PD-1) inhibitors in metastatic melanoma either permitted treatment for 2 years (pembrolizumab) or more (nivolumab). The optimal duration of therapy is currently unknown due to limited data, and shorter therapies may be effective.MethodsData of patients with metastatic cutaneous melanoma treated with single-agent PD-1 inhibitors at Huntsman Cancer Institute from January 1, 2015, to December 31, 2018, was reviewed to identify a continuous series of patients who made the joint decision with their provider to electively discontinue therapy at 1 year (>6 months and <18 months) in the setting of ongoing treatment response or disease stability. Patients were excluded if they received PD-1 inhibitors with other systemic therapy, had prior exposure to PD-1 therapy, or discontinued treatment due to disease progression or immune-related adverse event. Best objective response (BOR) per RECIST V.1.1 at treatment discontinuation, progression-free survival (PFS), and retreatment characteristics was analyzed.ResultsOf 480 patients who received PD-1 inhibitors, 52 met the inclusion criteria. The median treatment duration from first to the last dose was 11.1 months (95% CI 10.5 to 11.4). BOR was complete response in 13 (25%), partial response in 28 (53.8%), and stable disease in 11 (21.2%) patients. After a median follow-up of 20.5 months (range 3–49.2) from treatment discontinuation, 39 (75%) patients remained without disease progression, while 13 (25%) had progression (median PFS 3.9 months; range 0.7–30.9). On multivariable analysis, younger age, history of brain metastasis, and higher lactate dehydrogenase at the time of anti-PD-1 discontinuation were associated with recurrence. Patients with recurrent melanoma were managed with localized treatment, anti-PD-1 therapies, and BRAF-MEK inhibitors. All patients except one were alive at data cutoff.ConclusionIn this large real-world, observational cohort study, the majority of patients with metastatic melanoma after 1 year of anti-PD-1 therapy remained without progression on long-term follow-up. The risk of disease progression even in patients with residual disease on imaging was low. After prospective validation, elective PD-1 discontinuation at 1 year may reduce financial and immunotherapy-related toxicity without sacrificing outcomes.

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Association Between Duration of Immunotherapy and Overall Survival in Advanced Non–Small Cell Lung Cancer

et al. 2023

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ImportanceFor patients with advanced non–small cell lung cancer (NSCLC) treated with frontline immunotherapy-based treatment, the optimal duration of immune checkpoint inhibitor (ICI) treatment is unknown.ObjectiveTo assess practice patterns surrounding ICI treatment discontinuation at 2 years and to evaluate the association of duration of therapy with overall survival in patients who received fixed-duration ICI therapy for 2 years vs those who continued therapy beyond 2 years.Design, Setting, and ParticipantsThis retrospective, population-based cohort study included adult patients in a clinical database diagnosed with advanced NSCLC from 2016 to 2020, who received frontline immunotherapy-based treatment. The data cutoff was August 31, 2022; data analysis was conducted from October 2022 to January 2023.ExposuresTreatment discontinuation at 2 years (between 700 and 760 days, fixed duration) vs continued treatment beyond 2 years (greater than 760 days, indefinite duration).Main Outcomes and MeasuresOverall survival from 760 days was analyzed using Kaplan-Meier methods. Multivariable Cox regression that adjusted for patient-specific and cancer-specific factors was used to compare survival beyond 760 days between the fixed-duration group and the indefinite-duration group.ResultsOf 1091 patients in the analytic cohort who were still on ICI treatment at 2 years after exclusion criteria for death and progression were applied, 113 patients (median [IQR] age, 69 [62-75] years; 62 [54.9%] female; 86 [76.1%] White) were in the fixed-duration group, and 593 patients (median [IQR] age, 69 [62-76] years; 282 [47.6%] female; 414 [69.8%] White) were in the indefinite-duration group. Patients in the fixed-duration group were more likely to have a history of smoking (99% vs 93%; P = .01) and be treated at an academic center (22% vs 11%; P = .001). Two-year overall survival from 760 days was 79% (95% CI, 66%-87%) in the fixed-duration group and 81% (95% CI, 77%-85%) in the indefinite-duration group. There was no statistically significant difference in overall survival between patients in the fixed-duration and indefinite-duration groups, either on univariate (hazard ratio [HR] 1.26; 95% CI, 0.77-2.08; P = .36) or multivariable (HR 1.33; 95% CI, 0.78-2.25; P = .29) Cox regression. Approximately 1 in 5 patients discontinued immunotherapy at 2 years in the absence of progression.Conclusions and RelevanceIn a retrospective clinical cohort of patients with advanced NSCLC who were treated with immunotherapy and were progression-free at 2 years, approximately only 1 in 5 discontinued treatment. The lack of statistically significant overall survival advantage for the indefinite-duration cohort on adjusted analysis provides reassurance to patients and clinicians who wish to discontinue immunotherapy at 2 years.

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Continuous Versus 1-Year Fixed-Duration Nivolumab in Previously Treated Advanced Non–Small-Cell Lung Cancer: CheckMate 153

Cited by 143 publications

References 16 publications

Complete metabolic response in patients with advanced non-small cell lung cancer with prolonged response to immune checkpoint inhibitor therapy

Complete metabolic response in patients with advanced non-small cell lung cancer with prolonged response to immune checkpoint inhibitor therapy

Real-world experience with elective discontinuation of PD-1 inhibitors at 1 year in patients with metastatic melanoma

Association Between Duration of Immunotherapy and Overall Survival in Advanced Non–Small Cell Lung Cancer

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