Outcomes after progression of disease with anti–PD‐1/PD‐L1 therapy for patients with advanced melanoma

Abstract

Background Greater than one‐half of patients with melanoma who are treated with antibodies blocking programmed cell death protein 1 receptor (anti–PD‐1) experience disease progression. The objective of the current study was to identify prognostic factors and outcomes in patients with metastatic melanoma that progressed while they were receiving anti–PD‐1 therapy. Methods The authors evaluated 383 consecutively treated patients who received anti–PD‐1 for advanced melanoma between 2009 and 2019. Patient and disease characteristics at baseline and at the time of progression, subsequent therapies, objective response rate (ORR), overall survival, and progression‐free survival were assessed. Results Of 383 patients, 247 experienced disease progression. The median survival after progression was 6.8 months. There was no difference in survival noted after disease progression based on primary tumor subtype, receipt of prior therapy, or therapy type. However, significantly improved survival after disease progression correlated with clinical features at the time of progression, including normal lactate dehydrogenase, more favorable metastatic stage (American Joint Committee on Cancer eighth edition stage IV M1a vs M1b, M1c, or M1d), mutation status (NRAS or treatment‐naive BRAF V600 vs BRAF/NRAS wild‐type or treatment‐experienced BRAF‐mutant), decreasing tumor bulk, and progression at solely existing lesions. After progression, approximately 54.3% of patients received additional systemic therapy. A total of 41 patients received BRAF/MEK inhibition (ORR of 58.6%, including 70.4% for BRAF/MEK‐naive patients), 30 patients received ipilimumab (ORR of 0%), and 11 patients received ipilimumab plus nivolumab (ORR of 27.3%). Conclusions The current study identified prognostic factors in advanced melanoma for patients who experienced disease progression while receiving anti–PD‐1, including lactate dehydrogenase, stage of disease, site of disease progression, tumor size, and mutation status.

Retreatment with immune checkpoint inhibitors in solid tumors: a systematic review

“…In real-world clinical practice, systemic treatment including targeted therapy and chemotherapy are empirically applied, but the efficacy is limited. 7 – 10 Thus, considering the dynamic nature of the immune response and long-term benefit of ICIs, retreatment with the same or another ICI seems a suitable treatment option. Although several studies have evaluated the efficacy and safety of ICI retreatment, different regimens were administered to heterogeneous populations.…”

Radiological dynamics and SITC-defined resistance types of advanced melanoma during anti-PD-1 monotherapy: an independent single-blind observational study on an international cohort

“…Although no direct comparison between first line and post-PD-1 setting could be made for MAPKis and CTLA-4 monotherapy, they both demonstrated reasonable antitumor effect, similar to prior reports. 6 19–21 We also report that chemotherapy in the post-PD-1 scenario at these institutions was futile and is associated with similar lack of benefit as seen prior to the dawn of immunotherapy and targeted therapy. 22 …”

“…Imaging data at different time points have demonstrated constant correlations with survival outcomes. [3][4][5][6] However, as part of routine clinical practice, clinicians typically consider disease kinetics (fast vs slow growth/regression) to be one essential piece of information during therapeutic decision-making. At present, there are limited available data addressing the issue of tumor kinetics based on pretreatment and on-treatment radiographic imaging, change in tumor volume, and outcome for melanoma patients treated with anti-PD-1 monotherapy.…”

“…1 2 Emerging data demonstrate that radiological data taken at different static time points, for example, baseline, maximal response and disease progression (PD) were associated with survival outcomes of patients with melanoma under anti-PD-1 monotherapy. [3][4][5][6][7] Specifically, patients who achieved complete remission (CR) had the most durable survival benefit. 4 8 9 Therefore, in the absence of other biomarkers, 10 radiological response measurement is the most reliable and available data guiding therapeutic decision-making.…”

Biologic subtypes of melanoma predict survival benefit of combination anti-PD1+anti-CTLA4 immune checkpoint inhibitors versus anti-PD1 monotherapy

“…However, these studies were limited because they include a very small number of NRAS mutant patients who received anti-PD1 ICI 24 or analyzed only those patients who had already progressed on anti-PD1 ICI. 25 To our knowledge, the observation that NRAS mutations status can function as a predictive marker for anti-PD1 ICI outcomes is a novel finding.…”