Patterns of responses in metastatic NSCLC during PD-1 or PDL-1 inhibitor therapy: Comparison of RECIST 1.1, irRECIST and iRECIST criteria

Publication date: January 2018
Source:European Journal of Cancer, Volume 88
Author(s): M. Tazdait, L. Mezquita, J. Lahmar, R. Ferrara, F. Bidault, S. Ammari, C. Balleyguier, D. Planchard, A. Gazzah, J.C. Soria, A. Marabelle, B. Besse, C. Caramella
BackgroundImmune checkpoint inhibitors are an important tool in the therapeutic strategy against metastatic non–small cell lung cancer (NSCLC); however, radiological evaluation is challenging due to the emergence of atypical patterns of responses. Several evaluation criteria have been proposed, such as the Response Evaluation Criteria in Solid Tumours (RECIST), version 1.1, immune -related RECIST (irRECIST) and iRECIST, but have not been systematically compared in a homogeneous population.Patients and methodsWe conducted a monocentric retrospective analysis of consecutive advanced NSCLC patients treated with an anti–programmed cell death-1 or anti–program death-ligand 1. Response patterns and the discordance between RECIST 1.1, irRECIST and iRECIST guidelines were described, and associations of response patterns and clinical outcome were explored.ResultsOverall, 160 patients treated between February 2013 and October 2016 were included. Atypical responses were observed in 20 patients (13%), including eight pseudoprogressions (PsPDs) (5%) and 12 dissociated responses (8%). Thirteen of the 20 patients demonstrated clinical benefit. Per the RECIST 1.1, 37 patients (23%) showed an objective response or stable disease, and 123 patients (77%) exhibited progression. Eighty progressive patients were assessable for irRECIST and iRECIST: 15 patients were assessed differently; however, only three (3.8%) mismatches with a theoretical impact on the therapeutic decision were identified. Patients with PsPD or dissociated response had higher overall survival than patients with true progression.ConclusionAtypical responses (PsPD/dissociated response) occurred in 13% of NSCLC patients under immune checkpoint inhibitors. Based on survival analyses, the RECIST 1.1 evaluation underestimated the benefit of immune checkpoint inhibitors in 11% of the progressive patients. Immune-related RECIST and iRECIST identified these unconventional responses, with a 3.8% discrepancy rate.



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Pazopanib-Induced Cutaneous Leukocytoclastic Vasculitis: An Exclusion Diagnosis of a Multidisciplinary Approach

In phase II/III trials, cutaneous side effects of pazopanib were reported in less than 20% of patients, with only 1–3% being grade 3/4. We present a case of a 66-year-old man with a previous history of left nephrectomy for a stage II clear cell renal carcinoma. Approximately 18 months later, recurrent disease in the lungs, mediastinum, and left psoas and bulky abdominal/pelvic nodal metastasis were documented. He was initially treated with pazopanib 800 mg q.d. and 1 week after starting this therapy, the patient presented with palpable purpura on his ankles. These lesions regressed within 2 weeks off pazopanib, but had recurred 4 weeks after he resumed medication at 400 mg q.d. Biopsy of the lesions revealed leukocytoclastic vasculitis. Despite tumour response to therapy, pazopanib was discontinued with total resolution of this skin toxicity within 2 weeks of his cutaneous toxicity. To the best of our knowledge, we report a rare yet significant cutaneous adverse reaction to pazopanib.
Case Rep Oncol 2017;10:1041–1049

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Successful Resection of G719X-Positive Pleomorphic Carcinoma after Afatinib Treatment

We report a case of pleomorphic carcinoma with exon 18 mutation (G719X) of the epidermal growth factor receptor (EGFR), which showed good response to afatinib and resulted in successful resection. To our knowledge, this is the first report on the use of afatinib for pleomorphic carcinoma followed by the surgical resection. The patient was a 59-year-old woman, who visited our hospital because chest computed tomography showed a 28 × 28-mm nodule in the left upper lobe. Bronchoscopy was performed and the histological findings of transbronchial biopsy revealed adenosquamous carcinoma positive for G719X mutation in exon 18 of the EGFR. Since fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography revealed a positive accumulation in the bilateral hilar and mediastinal lymph nodes, the disease was diagnosed as cT1bN3M0, stage IIIB. After 3 months of afatinib therapy, FDG accumulation in primary tumor was almost gone. However, FDG accumulation in lymph nodes remained unchanged. Video-assisted thoracic surgery was planned for further diagnostic information and left upper lobectomy with mediastinal lymph node dissection was performed. The resected tumor included adenocarcinoma, squamous cell carcinoma, and spindle cell components, without lymph node metastasis. Thus, the disease was diagnosed as pleomorphic carcinoma (pT2aN0M0, stage IB). All components in the resected specimen had the same G719X mutation in exon 18 of the EGFR. The patient has shown no signs of recurrence at 1 year after the operation. The present case indicates the possibility of minor EGFR mutations in pleomorphic carcinoma and successful outcome by the use of afatinib and surgical resection.
Case Rep Oncol 2017;10:1035–1040

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Risk of fatigue in cancer patients receiving anti-EGFR monoclonal antibodies: results from a systematic review and meta-analysis of randomized controlled trial

Abstract

Background

To evaluate the association between fatigue and anti-epidermal growth factor receptor monoclonal antibodies (anti-EGFR MAbs), we conducted the first meta-analysis to access the incidence and risk of fatigue associated with anti-EGFR MAbs.

Methods

Electronic databases were searched for randomized controlled trials (RCTs) published up to February 2017. Eligible studies were selected according to PRISMA statement. Incidence rates, risk ratio (RRs), and 95% confidence intervals (CIs) were calculated using fixed-effects or random-effects models. Outcomes of quality were summarized in accordance with the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology.

Results

Thirty-five RCTs (including 15,622 patients) were included; median follow-up ranged from 8.1 to 71.4 months, and the fatigue events were recorded and graded according to the Common Toxicity Criteria for Adverse Events version 2.0 or 3.0 in most of the included trials. For patients receiving anti-EGFR MAbs, the overall incidence of all-grade and high-grade fatigue was 54.1% and 10.5%, respectively. Compared with control, anti-EGFR MAbs significantly increased the risk of all-grade fatigue (RR 1.10, 95% CI, 1.05–1.14, moderate-quality evidence) and high-grade fatigue (RR 1.31, 95% CI, 1.19–1.45, moderate-quality evidence). No significant differences among subgroup analyses (anti-EGFR MAbs, tumor type, and median follow-up) on high-grade fatigue were observed. No evidence of publication bias was observed.

Conclusion

The present study suggested that anti-EGFR MAbs may increase the risk of fatigue in cancer patients.

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Risk of fatigue in cancer patients receiving anti-EGFR monoclonal antibodies: results from a systematic review and meta-analysis of randomized controlled trial

Abstract

Background

To evaluate the association between fatigue and anti-epidermal growth factor receptor monoclonal antibodies (anti-EGFR MAbs), we conducted the first meta-analysis to access the incidence and risk of fatigue associated with anti-EGFR MAbs.

Methods

Electronic databases were searched for randomized controlled trials (RCTs) published up to February 2017. Eligible studies were selected according to PRISMA statement. Incidence rates, risk ratio (RRs), and 95% confidence intervals (CIs) were calculated using fixed-effects or random-effects models. Outcomes of quality were summarized in accordance with the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology.

Results

Thirty-five RCTs (including 15,622 patients) were included; median follow-up ranged from 8.1 to 71.4 months, and the fatigue events were recorded and graded according to the Common Toxicity Criteria for Adverse Events version 2.0 or 3.0 in most of the included trials. For patients receiving anti-EGFR MAbs, the overall incidence of all-grade and high-grade fatigue was 54.1% and 10.5%, respectively. Compared with control, anti-EGFR MAbs significantly increased the risk of all-grade fatigue (RR 1.10, 95% CI, 1.05–1.14, moderate-quality evidence) and high-grade fatigue (RR 1.31, 95% CI, 1.19–1.45, moderate-quality evidence). No significant differences among subgroup analyses (anti-EGFR MAbs, tumor type, and median follow-up) on high-grade fatigue were observed. No evidence of publication bias was observed.

Conclusion

The present study suggested that anti-EGFR MAbs may increase the risk of fatigue in cancer patients.

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