Elsevier

Cancer Treatment Reviews

Volume 59, September 2017, Pages 71-78
Cancer Treatment Reviews

Systematic or Meta-analysis Studies
Atypical responses in patients with advanced melanoma, lung cancer, renal-cell carcinoma and other solid tumors treated with anti-PD-1 drugs: A systematic review

https://doi.org/10.1016/j.ctrv.2017.07.002Get rights and content

Highlights

  • Atypical responses to anti-PD-1 therapy were evaluated in 19 clinical trials.

  • 151 responses after initial progression were observed in 2400 patients (6%).

  • Some patients may derive benefit from extended anti-PD-1 therapy beyond progression.

Summary

Anti-programmed death receptor 1 (PD-1) drugs nivolumab and pembrolizumab were recently approved for the treatment of advanced melanoma and other solid tumors. Atypical patterns of response (i.e. tumor shrinkage or stabilization after initial progression) were observed in about 10% of metastatic melanoma patients treated with anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) drug ipilimumab and were associated with improved survival; however, the rate of atypical response patterns to anti-PD-1 therapy is not clear. An electronic search was performed to identify clinical trials evaluating response to anti-PD-1 therapy with nivolumab and pembrolizumab in patients with advanced solid tumors.

Thirty-eight studies were included in our analysis for a total of 7069 patients with advanced cancer treated with anti-PD-1 therapy. Responses were evaluated by unconventional response criteria in 19 trials and were observed for all cancer types but tumors with mismatch-repair deficiency and head and neck squamous cell carcinoma. Overall, 151 atypical responses were observed in 2400 patients (6%) evaluated by unconventional response criteria.

The results of our systematic review highlight the clinical relevance of unconventional responses to anti-PD-1 therapy and support further investigation into the development of tools that may assist evaluation of the antitumor activity of immunotherapy.

Section snippets

Background

Immune checkpoint inhibitors have emerged as effective treatments for melanoma and other cancers. Ipilimumab, a fully human monoclonal antibody that blocks cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), was the first immune checkpoint inhibitor approved by the regulatory authorities for the treatment of melanoma; more recently, anti-programmed death receptor 1 (PD-1) drugs nivolumab and pembrolizumab were approved for the treatment of melanoma and other cancers, such as non-small-cell

Methods

Preferred Reporting Items for Systematic Reviews and meta-Analyses (PRISMA) guidelines were used for the conduct and reporting of this systematic review [2].

Study characteristics

Thirty-eight studies were included in our analysis for a total of 7069 patients with advanced cancer treated with anti-PD-1 therapy [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49]. Treatment regimens included pembrolizumab and nivolumab at different dosages, nivolumab plus a

Discussion

Immune checkpoint inhibitors demonstrated significant anticancer activity in many cancer types and are likely to play a major role in cancer treatment in the future. Ipilimumab, which improved survival in advanced melanoma patients, was the first immune checkpoint inhibitor approved by regulatory agencies; anti-PD-1 agents were recently approved for melanoma, NSCLC, RCC, head and neck squamous cell carcinoma and are in clinical development for more than 30 tumor types. Atypical patterns of

Conflict of interest statement

All authors have no financial interest in any of the products, devices, or drugs mentioned in this article. FS received lecture fees from Bristol-Myers Squibb, Novartis, Roche, MSD; PQ received lecture fees and served on advisory board for Bristol-Myers Squibb, Novartis, Roche and MSD.

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