IMPORTANCE For patients with cancer treated with palliative intent, quality of life (QOL) is a critical aspect of treatment decision-making, alongside survival. However, regulatory approval can be based solely on survival measures or antitumor activities, without QOL evidence. OBJECTIVE To investigate whether recently approved oncology therapies demonstrate clinically meaningful improvements in QOL. EVIDENCE REVIEW This systematic review study identified oncology drug indications approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) from January 2006 to December 2017 and supporting clinical trials (QOL publications identified to October 2019). Indications were evaluated for the presence of published QOL evidence; QOL benefits according to the American Society of Clinical Oncology Value Framework version 2.0 (ASCO-VF) and European Society of Medical Oncology Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS) QOL bonus criteria; and clinically meaningful improvements in QOL beyond minimal clinically important differences. Hematology trials were not evaluated by ESMO-MCBS. Associations between QOL evidence and approval year were examined using logistic regression models. FINDINGS In total, 214 FDA-approved (77 [36%] hematological) and 170 EMA-approved (52 [31%] hematological) indications were included. QOL evidence was published for 40% and 58% of FDAand EMA-approved indications, respectively. QOL bonus criterion for ASCO-VF and ESMO-MCBS was met in 13% and 17% of FDA-approved and 21% and 24% of EMA-approved indications, respectively. Clinically meaningful improvements in QOL beyond minimal clinically important differences were noted in 6% and 11% of FDA-and EMA-approved indications, respectively. Availability of published QOL evidence at the time of approval increased over time for EMA (odds ratio [OR], 1.13; P = .03), however not for FDA (OR, 1.10; P = .12). Over time, no increase in awarded QOL bonuses or clinically meaningful improvements in QOL were found. CONCLUSIONS AND RELEVANCE The findings of this systematic review suggest that approved systemic oncology therapies often do not have published evidence to suggest QOL improvement, despite its recognized importance. Of indications with evidence of statistical improvement, few have demonstrated clinically meaningful improvements.

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Background: Restricted mean survival time (RMST) overcomes limitations of current measures of survival benefits because it directly captures information of the entire area under Kaplan-Meier survival curves. Using RMST difference (absolute survival benefit) and RMST ratio (relative survival benefit), we quantified the magnitude of survival benefits of recent oncology drugs and compared immunotherapies with nonimmunotherapies. Methods: Kaplan-Meier curves were extracted from phase II/III randomized controlled trials used by the FDA for oncology drug approvals from January 2011 through November 2017 with overall survival (OS) or progression-free survival (PFS) as primary endpoints. RMST differences, ratios, and their 95% confidence intervals were meta-analyzed to estimate absolute and relative survival benefits of contemporary oncology drugs and to compare immunotherapies with nonimmunotherapies. Meta-regression was conducted to adjust for potential confounders. Results: Ninety-four trials with a total of 51,639 patients were included. Overall absolute survival benefits (RMST differences) were 1.55 months for OS (95% CI, 1.32–1.77) and 2.99 months for PFS (95% CI, 2.65–3.33). Overall relative survival benefits (RMST ratios) were 1.11 for OS (95% CI, 1.09–1.13) and 1.42 for PFS (95% CI, 1.36–1.48). Immunotherapy absolute PFS benefit was less than that of nonimmunotherapy (1.56 vs 3.23 months), whereas immunotherapy absolute OS benefit was larger than that of nonimmunotherapy by 0.59 months (2.02 vs 1.43 months). Adjusted OS RMST difference was 0.91 months greater for immunotherapy than for nonimmunotherapy after adjusting for confounders. Conclusions: Absolute survival benefits of recent oncology drugs are modest. Survival benefits of immunotherapies are not dramatically superior to those of nonimmunotherapies. Routine reporting and use of RMST may help patients, physicians, and payers make more informed and responsible decisions regarding the care of patients with cancer.

9087 Background: Pembrolizumab (P) has replaced chemotherapy (C) as first-line treatment for advanced non-small cell lung cancer (NSCLC) with tumor PD-L1 expression > / = 50%. Among PD-L1 unselected patients, P+C is superior to C alone. This network meta-analysis compared P alone with P+C in patients with > / = 50% PD-L1 positive NSCLC. Methods: An indirect network was constructed to compare P and P+C through the control arms of the Keynote 024, 189 and 407 (PD-L1 > / = 50% subgroup) trials. Baseline characteristics and chemotherapy outcomes were examined for heterogeneity. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and toxicities including immune-related adverse events (irAE) were extracted from trial results. Toxicity results were unavailable for the PD-L1 > / = 50% subgroups of KN 189 & 407, so overall study results were used. Survival outcomes are expressed as hazard ratios (HRs) or restricted mean survival time (RMST) ratios, and toxicity and ORR as risk difference (RD). Results: 507 patients were included: 154 on P, 430 on C and 483 on P+C. Patient characteristics across trials were similar in age, sex, performance status and smoking history. All trials had similar chemotherapy outcomes (PFS 6, 4.9, 4.8 mos) suggesting similar populations. Network meta-analysis showed no difference between P+C and C alone in OS (HR 0.85, 95%CI 0.45-1.59, p = 0.60) or PFS (HR 0.73, 95%CI 0.48-1.1, p = 0.13), but P+C was associated with higher ORR (+16.9%, 95%CI 0.7-33%, p = 0.04). RMST analysis suggested fewer early PFS events with P+C (0-6 mo RMST ratio 1.25, RMST difference 1.02 mo, p = 0.002), with the difference disappearing at 1 year (0-12 mo RMST ratio 1.16, p = 0.07). No difference in RMST for OS was found. Overall toxicities, hematologic and grade 3-5 toxicities were higher with P+C compared with P alone (table). Conclusions: Among patients with > / = 50% PD-L1 positive NSCLC, P+C did not improve OS or PFS compared with P alone, but was associated with higher ORR. RMST analysis suggested fewer early progression events using P+C. [Table: see text]