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PD1/PD-L1blockers trigger metastases

Drug Developers dealing with PD1-PDL1 checkpoint inhibitors must consider new safety problems associated with the hyped cancer meds. 

A retrospective study on 377 patients with advanced non small cell lung cancer (NSCLC) who received PD-1 blockers as second-line therapy or later indicates that therapy outcomes are worse than those observed with classical chemotherapeutics (JAMA Oncology). 

After median follow-up of 12 months, 13.8% of patients had hyperproliferative disease (HPD), which is characterised by accelerated tumour proliferation, tumour outgrowth, and worse prognosis, patients experiencing HPD within the first six weeks of PD-1/PD-L1 inhibitor treatment had significantly lower overall survival (OS 3.4 months) vs patients with progressive disease (OS 6.2 months). In contrast, only 3 in 59 patients receiving chemotherapy (5.1%) developed HPD.

“Our study suggests that HPD is more common with PD-1/PD-L1 inhibitors compared with chemotherapy in pretreated patients with NSCLC and is also associated with high metastatic burden and poor prognosis in patients treated with PD-1/PD-L1 inhibitors,“ conclude the authors, headed by Caroline Caramella from French Gustave Roussy cancer centre in Villejuif. As HPD previously was reported in 9% of advanced cancers  and in 29% of patients with head and neck cancer, they say that “additional studies are needed to determine the molecular mechanisms involved.“

Patients investigated had received either the anti-PD-1 mAbs nivolumab (Bristol-Myers Squibb) or pembrolizumab (Merck & Co.) or the anti-PD-L1 mAbs atezolizumab (Roche) or durvalumab from AstraZeneca plc

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