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•In a naturalistic pain clinic population, 61% reported clinically relevant pain-related injustice.•Higher levels of perceived injustice were consistently associated with adverse pain outcomes.•Injustice was associated with recovery and deterioration at follow-up, but not in adjusted models.

Immune checkpoint inhibitors have shown efficacy against metastatic triple-negative breast cancer (mTNBC) but only for PD-L1positivedisease. The randomized, placebo-controlled ALICE trial (NCT03164993, 24 May 2017) evaluated the addition of atezolizumab (anti-PD-L1) to immune-stimulating chemotherapy in mTNBC. Patients received pegylated liposomal doxorubicin (PLD) and low-dose cyclophosphamide in combination with atezolizumab (atezo-chemo; n= 40) or placebo (placebo-chemo; n= 28). Primary endpoints were descriptive assessment of progression-free survival in the per-protocol population (>3 atezolizumab and >2 PLD doses; n= 59) and safety in the full analysis set (FAS; all patients starting therapy; n= 68). Adverse events leading to drug discontinuation occurred in 18% of patients in the atezo-chemo arm (7/40) and in 7% of patients in the placebo-chemo arm (2/28). Improvement in progression-free survival was indicated in the atezo-chemo arm in the per-protocol population (median 4.3 months versus 3.5 months; hazard ratio (HR) = 0.57; 95% confidence interval (CI) 0.33–0.99; log-rank P= 0.047) and in the FAS (HR = 0.56; 95% CI 0.33–0.95; P= 0.033). A numerical advantage was observed for both the PD-L1positive(n= 27; HR = 0.65; 95% CI 0.27–1.54) and PD-L1negativesubgroups (n= 31; HR = 0.57, 95% CI 0.27–1.21). The progression-free proportion after 15 months was 14.7% (5/34; 95% CI 6.4–30.1%) in the atezo-chemo arm versus 0% in the placebo-chemo arm. The addition of atezolizumab to PLD/cyclophosphamide was tolerable with an indication of clinical benefit, and the findings warrant further investigation of PD1/PD-L1 blockers in combination with immunomodulatory chemotherapy.