Lorlatinib Effectiveness and Quality-of-Life in Patients with ALK-Positive NSCLC Who Had Failed Second-Generation ALK Inhibitors: Canadian Real-World Experience.

Lorlatinib is the only targeted therapy approved in Canada to treat patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) whose tumor has progressed despite treatment with second-generation ALK tyrosine kinase inhibitor (TKI), a patient population with high unmet need and lack of publicly reimbursed targeted treatments in Canada. We prospectively examined the real-world effectiveness and impact of lorlatinib on quality-of-life in 59 lorlatinib-treated patients, characterized as: median age of 62.0 years; 47.5% were female; 32.2% had central nervous system metastases; 50.8% had 2+ prior ALK TKI lines; and alectinib was the most common ALK TKI (72.9%) administered before lorlatinib, including 44.1% who received first-line alectinib. With a median follow-up of 15.3 months (IQR: 6.2-19.2), median time-to-treatment discontinuation of lorlatinib was 15.3 months (95% CI: 7.9-not reached), with 54.2% (95% CI: 40.8-65.9%) of patients without treatment discontinuation at 12 months. At baseline, the mean health utility score (HUS) was 0.744 (SD: 0.200). At 3 months, patients receiving lorlatinib demonstrated a 0.069 (95% CI: 0.020-0.118; p = 0.007) average HUS increase over baseline; HUS was maintained at 6 and 12 months. Thus, patients with ALK-positive NSCLC post second-generation ALK TKI remained on lorlatinib for a meaningful duration of time while their quality-of-life was preserved.

Impact of Tofacitinib on Components of the ACR Response Criteria: Post Hoc Analysis of Phase III and Phase IIIb/IV Trials.

OBJECTIVE: To evaluate the effect of tofacitinib (TOF) on American College of Rheumatology (ACR) response criteria components in patients with rheumatoid arthritis (RA). METHODS: This post hoc analysis pooled data from RA phase III randomized controlled trials (RCTs) assessing TOF 5 or 10 mg BID, adalimumab (ADA), or placebo, with conventional synthetic disease-modifying antirheumatic drugs, and a phase IIIb/IV RCT assessing TOF 5 mg BID monotherapy, TOF 5 mg BID with methotrexate (MTX), or ADA with MTX. Outcomes included proportions of patients achieving ACR20/50/70 responses and ≥ 20/50/70% improvement rates in ACR components at week 2 and months 1, 3, and 6; and mean percent improvement in ACR components and Clinical or Simplified Disease Activity Index (CDAI or SDAI) low disease activity or remission rates, at month 3, for ACR20/50/70 responders. RESULTS: Across treatment groups, ≥ 20/50/70% improvement rates were numerically higher for most physician- vs patient-reported measures. In phase III RCTs, at earlier timepoints, ≥ 50/70% improvements in patient global assessment of disease activity, pain, and physician global assessment were similar. Among ACR20 responders receiving TOF, mean percent improvements for tender and swollen joint counts were > 70% at month 3. CDAI/SDAI remission was achieved at month 3 by 27.8-45.0% of ACR70 responders receiving TOF. CONCLUSION: Among ACR20 responders treated with TOF, physician-reported components particularly exceeded 20% response improvement. At month 3, disease state generally did not corroborate ACR70 response criteria. Divergences between physician- and patient-reported measures highlight the importance of identifying appropriate patient-reported outcome targets to manage RA symptoms in clinical practice. (ClinicalTrials.gov: NCT00847613/NCT00856544/NCT00853385/NCT02187055).