Non-small cell lung cancer with EGFR exon 20 insertion mutation: a systematic literature review and meta-analysis of patient outcomes.

INTRODUCTION: EGFR exon 20 insertion mutation-positive non-small cell lung cancer (NSCLC) is rare, has a poor prognosis, and outcomes are not fully established. We describe and evaluate outcomes from real-world and clinical evidence in these patients. METHODS: A systematic literature review (SLR) identified interventional and real-world evidence (RWE) studies reporting clinical outcomes for EGFR exon 20 insertion mutation-positive NSCLC. Meta-analyses were conducted by line of therapy to synthesize pooled survival and response outcomes across RWE. Published evidence from interventional studies was summarized individually. RESULTS: The SLR identified 23 RWE and 19 original interventional studies. In the meta-analysis of RWE, pooled response and survival outcomes were low for first-line EGFR-tyrosine kinase inhibitors (TKIs) and immuno-oncology (IO) agents. First-line chemotherapy resulted in a pooled ORR 25.7%, pooled PFS 5.6 months, and pooled OS 18.3 months. Pooled outcomes were further reduced in second or later lines (≥2 L): pooled ORR was 5.0%, 3.3%, and 13.9%; pooled PFS was 2.1 months, 2.3 months, and 4.4 months; and pooled OS was 14.1 months, 8.8 months, and 17.1 months (not a pooled result) for EGFR-TKIs, IO agents, and chemotherapy, respectively. Interventional studies reported outcomes for TKIs (mobocertinib, poziotinib, osimertinib, afatinib, CLN-081, DZD9008), a monoclonal antibody (amivantamab), and a heat shock protein 90 inhibitor (luminespib). While there is limited RWE for the recently approved agents mobocertinib and amivantamab, which specifically target exon 20 insertion mutations, interventional evidence supports their potential as effective treatment options. CONCLUSIONS: Conventional treatments used in patients with EGFR exon 20 insertion mutation-positive NSCLC have limited efficacy, though chemotherapy appeared to be associated with better response and survival outcomes than non-exon 20 targeting EGFR-TKIs and IO agents. This supports the need to identify EGFR exon 20 insertion mutations as the availability of new targeted treatments may offer additional therapeutic options to these patients.

Comparative Effectiveness of Remestemcel-L-rknd versus Ruxolitinib in Pediatric Patients with Steroid-Refractory Acute Graft-Versus-Host Disease using Simulated Treatment Comparisons.

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) can be a lifesaving treatment for hematologic malignancies, but acute graft-versus-host-disease (aGVHD) is a potentially deadly adverse effect experienced by up to half of allo-HSCT recipients. Inadequate response to steroid therapy for aGVHD is associated with poor prognosis and high mortality, including among pediatric patients, who are the focus of this study. Ruxolitinib and remestemcel-L-rknd were evaluated for the treatment of steroid-refractory (SR) aGVHD in two separate single-arm trials. To effectively compare the safety and efficacy of these treatments without a head-to-head trial, a simulated treatment comparison (STC) was conducted. Methods: Regression techniques were used to adjust individual patient-level data from the remestemcel-L-rknd trial to mutually reported baseline characteristics from the ruxolitinib trial. Outcomes of interest included a 28-day overall response rate (ORR), a 28-day ORR in the grade III-IV aGVHD population, and adverse events (AEs). Results: In the full populations, the STC of risk ratios (RRs) found treatment with remestemcel-L-rknd to be associated with a numerical but not statistically significant improvement in the 28-day ORR versus ruxolitinib. In the grade III-IV aGVHD sub-group, the STC showed significantly improved 28-day ORR for remestemcel-L-rknd versus ruxolitinib (P=0.04). Remestemcel-L-rknd was also associated with improved safety outcomes (P<0.05) in 17 out of 30 AEs, including hematologic events, peripheral edema, muscular weakness, nausea, back pain, and fatigue. Conclusion: Remestemcel-L-rknd was associated with significant improvements in day 28 ORR compared with ruxolitinib in patients with severe (grade III-IV) SR aGVHD. Across all grades of SR aGVHD, remestemcel-L-rknd was associated with fewer all-grade treatment-emergent adverse events (TEAEs) (27/30) available for comparison, including the majority reaching statistical significance.

Health-related quality of life and utility outcomes with selinexor in relapsed/refractory diffuse large B-cell lymphoma.

Aim: Evaluate health-related quality of life (HRQoL) and health utility impact of single-agent selinexor in heavily pretreated patients with relapsed/refractory diffuse large B-cell lymphoma. Patients & methods: Functional Assessment of Cancer Therapy (FACT) - Lymphoma and EuroQoL five-dimensions five-levels data collected in the single-arm Phase IIb trial SADAL (NCT02227251) were analyzed with mixed-effects models. Results: Treatment responders maintained higher FACT - Lymphoma (p ≤ 0.05), FACT - General (p < 0.05) and EuroQoL five-dimensions five-levels index scores (p < 0.001) beginning in cycle 3. The estimated difference in health state utilities for treatment response and progressive disease was both statistically significant and clinically meaningful (mean difference: 0.07; p = 0.001). Conclusion: In patients with relapsed/refractory diffuse large B-cell lymphoma, objective response to selinexor was associated with HRQoL maintenance, reduction in disease-related HRQoL decrements and higher health utilities.

Lay abstract This work examined quality of life (QoL) among patients with relapsed/refractory diffuse large B-cell lymphoma with two to five prior therapies who received single-agent selinexor in the SADAL clinical trial. Analysis of patient-reported Functional Assessment of Cancer Therapy ­ Lymphoma and EuroQoL five-dimensions five-levels data showed that patients who had objective clinical response to selinexor maintained their QoL over the course of treatment. Grade ≥3 adverse events and serious adverse events were not associated with clinically meaningful negative QoL impacts. Clinical trial registration: NCT02227251 (ClinicalTrials.gov).