Emilie Lanoy

Introduction: Using three categories of stages of HIV disease at access to care (advanced, intermediate, early HIV disease), we explored the impact of delayed access on the risk of death at up to 5 years and whether progress in antiretroviral regimens has mitigated this impact. Methods: Adults from the French Hospital Database on HIV (ANRS CO4-FHDH) cohort with HIV-1 infection and first access to care during 2002–2021 were included. To study the impact of the stage of HIV disease at first access to care on the risk of death, only participants included from 2002 to 2016 were analysed to allow for at least 5 years of follow-up until 31 December 2021. Fine and Gray competing risk models considering lost to follow-up as a competing event were used adjusting for age, gender, mode of acquisition, region of origin, time between diagnosis and access to care, period of access to care (2002–2013 vs 2014–2016). Results: Among the 64 400 people living with HIV included, 18 305 (28.4%) had advanced and 13 042 (20.3%) intermediate HIV disease. The 5-year cumulative incidence of death was estimated as 1.8% (95% CI 1.7% to 1.9%) overall, from 0.9% (0.8% to 1.0%) for those with early HIV disease to 6.0% (5.4% to 6.7%) for those with AIDS. People with AIDS had a much higher risk of death than those with early HIV disease, with a sub-distribution HR (sHR) of 18.4 (95% CI 12.0 to 28.4) in the first 6 months of follow-up, which remained significant at 48–60 months: sHR=2.1 (1.3 to 3.3). The risk of death was higher for the other categories of advanced HIV disease but to a smaller extent. The risk of death was not statistically different depending on the calendar period. Conclusions: Delayed access to care remains associated with an elevated risk of death, even after 48 months. There was no significant improvement in the risk of death after 2014 when immediate initiation of combined antiretroviral therapy was recommended and integrase strand transfer inhibitor-based regimens became the preferred first-line.

Background Cemiplimab an anti-programmed cell death receptor-1 antibody, was approved by the FDA and EMA for patients with locally advanced cutaneous squamous cell carcinoma (laCSCC) ineligible for curative surgery/radiotherapy or with metastatic (m) CSCC. TOSCA study evaluated the real-world effectiveness and safety of cemiplimab compared to historical systemic therapies (HSTs). Methods TOSCA (NCT05302297) was a large French retrospective, multicenter study comparing patient with la/mCSCC treated with cemiplimab via the early access program (EAP, 2018–2019) or HST (2013–2018). The primary endpoint was overall survival (OS); secondary endpoints were progression-free survival (PFS), duration of response (DoR), overall response rate (ORR), and safety. Effectiveness analysis using inverse probability weighting included a trial-like cohort of only immunocompetent patients meeting the EAP criteria to emulate a randomized clinical trial; safety analysis included all real-life patients. Findings The study included 280 real-life patients (cemiplimab: n=147; HST: n=133). The primary effectiveness analysis included a trial-like cohort (cemiplimab: n=129; HST: n=70; median age: 81 and 78 years, respectively). Median follow-up was 20 and 10 months in the cemiplimab and HST arms, respectively; median OS was 21.2 and 9.8 months, respectively (HR 95% CI: 0.57 [0.45–0.73]; P<0.0001); median PFS was 13.7 and 5.3 months, respectively (HR [95% CI]: 0.57 [0.43–0.76]; P=0.0001). Adverse drug reactions occurred in 27% of cemiplimab patients and 33% of HST patients. . Interpretation TOSCA demonstrated better survival and response outcomes for cemiplimab versus HST in la/mCSCC; emphasizing, the importance of rigorous retrospective studies in the absence of standard comparative trials. Funding Sanofi.

Sup Data Table S1: Characteristic features of long responder patients Sup Data Figure S1: a: PFS and OS from the first objective response assessed for responder patients; b: PFS and OS from the first objective response assessed for partial responders; c: OS and PFS from the first complete response assessed (crPFS and crOS) Sup Data Figure S2: Risk of relapse upon therapy discontinuation function of therapy duration Sup Data Figure S3: Survival from relapse and PFS from OR of secondary refractory disease Sup Data Figure S4: PFS from OR of secondary refractory disease function of tumor type Sup Data Table S2: Characteristics of secondary refractory disease Sup Data Table S3: Characteristics of long survival after immunotherapy initiation with progression first response/stable disease then progression: n=30 (%) Sup Data Table S4: Objective response rate (ORR) as a function of tumor type (%) Sup Data Figure S5a: PFS function of RMH score Sup Data Figure S5b: OS function of the RMH score Sup Data Figure 6: a: Overall survival function of NLR, b: Overall survival for patients presenting progressive disease as best response function of the NLR, c: Overall survival for patients presenting stable disease as best response function of the NLR d: Overall survival for patients presenting objective response as best response function of the NLR Sup Data Figure S7: a: Response function of neutrophil and lymphocyte counts, b: comparison of lymphocyte count function of response, c: comparison of neutrophil count function of response

Purpose:Anti–PD-(L)1 can provide overall survival (OS) benefits over conventional treatments for patients with many different cancer types. However, the long-term outcome of cancer patients responding to these therapies remains unknown. This study is an exploratory study that aimed to describe the long-term survival of patients responding to anti–PD-(L)1 monotherapy across multiple cancer types.Patients and Methods: Data from patients treated with an anti–PD-(L)1 monotherapy in a phase I trial at Gustave Roussy were retrospectively analyzed over a period of 5 years. All cancer types (n = 19) were included. Clinical and biological factors associated with response, long-term survival, and secondary refractory disease were studied.Results:Among 262 eligible patients, the overall objective response rate was 29%. The median progression-free survival of responder patients (RP) at 3 months was 30 months, and the median OS of RP was not reached after a median follow-up of 34 months. In RPs, 3- and 5-year OS percentages were 84% and 64%, respectively. No death occurred in the 21 complete responders (CR) during the overall follow-up. However, many partial responders (PR) showed subsequent tumor relapses to treatment. Long responders (response ≥2 years) represented 11.8% of the overall population. These findings should be validated in further prospective studies.Conclusions:There are currently no differences in therapeutic strategies between CRs and PRs to anti–PD-(L)1. We found a striking difference in OS between these two types of responses. Our results are in favor of evaluating patient stratification strategies and intensification of treatments when tumor lesions of a partial responder to immunotherapy stop improving.See related commentary by Cohen and Flaherty, p. 910

Sup Data Table S1: Characteristic features of long responder patients Sup Data Figure S1: a: PFS and OS from the first objective response assessed for responder patients; b: PFS and OS from the first objective response assessed for partial responders; c: OS and PFS from the first complete response assessed (crPFS and crOS) Sup Data Figure S2: Risk of relapse upon therapy discontinuation function of therapy duration Sup Data Figure S3: Survival from relapse and PFS from OR of secondary refractory disease Sup Data Figure S4: PFS from OR of secondary refractory disease function of tumor type Sup Data Table S2: Characteristics of secondary refractory disease Sup Data Table S3: Characteristics of long survival after immunotherapy initiation with progression first response/stable disease then progression: n=30 (%) Sup Data Table S4: Objective response rate (ORR) as a function of tumor type (%) Sup Data Figure S5a: PFS function of RMH score Sup Data Figure S5b: OS function of the RMH score Sup Data Figure 6: a: Overall survival function of NLR, b: Overall survival for patients presenting progressive disease as best response function of the NLR, c: Overall survival for patients presenting stable disease as best response function of the NLR d: Overall survival for patients presenting objective response as best response function of the NLR Sup Data Figure S7: a: Response function of neutrophil and lymphocyte counts, b: comparison of lymphocyte count function of response, c: comparison of neutrophil count function of response

Purpose:Anti–PD-(L)1 can provide overall survival (OS) benefits over conventional treatments for patients with many different cancer types. However, the long-term outcome of cancer patients responding to these therapies remains unknown. This study is an exploratory study that aimed to describe the long-term survival of patients responding to anti–PD-(L)1 monotherapy across multiple cancer types.Patients and Methods: Data from patients treated with an anti–PD-(L)1 monotherapy in a phase I trial at Gustave Roussy were retrospectively analyzed over a period of 5 years. All cancer types (n = 19) were included. Clinical and biological factors associated with response, long-term survival, and secondary refractory disease were studied.Results:Among 262 eligible patients, the overall objective response rate was 29%. The median progression-free survival of responder patients (RP) at 3 months was 30 months, and the median OS of RP was not reached after a median follow-up of 34 months. In RPs, 3- and 5-year OS percentages were 84% and 64%, respectively. No death occurred in the 21 complete responders (CR) during the overall follow-up. However, many partial responders (PR) showed subsequent tumor relapses to treatment. Long responders (response ≥2 years) represented 11.8% of the overall population. These findings should be validated in further prospective studies.Conclusions:There are currently no differences in therapeutic strategies between CRs and PRs to anti–PD-(L)1. We found a striking difference in OS between these two types of responses. Our results are in favor of evaluating patient stratification strategies and intensification of treatments when tumor lesions of a partial responder to immunotherapy stop improving.See related commentary by Cohen and Flaherty, p. 910