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Background: Elderly patients are underrepresented in clinical trials, particularly in early-phase studies. Our study assessed the safety and efficacy of novel anti-cancer treatments investigated in early-phase clinical trials, comparing outcomes between younger and elderly patients., Methods: This retrospective study analyzed data from patients enrolled in phase I/II trials at our center between January 2014 and April 2021. We evaluated clinicopathologic characteristics, toxicity, and clinical efficacy, categorizing patients into younger (≤ 65 years) and elderly (> 65 years) groups., Results: 419 patients were included with a median age of 56 years. Among these, 107 (26 %) were older than 65 years. Predominant cancers included breast (48 %), lung (10 %), and melanoma (5 %). Patients were treated in 64 trials, predominantly receiving immunotherapy-based (47 %) or targeted therapy-based (45 %) treatment. Elderly presented with poorer ECOG performance status (P = 0.001) and had fewer prior therapy lines (P = 0.01) than younger patients. Grade ≥ 3 adverse events (AEs) were similar across age groups (31 % younger vs 33 % elderly; P = 0.7), including in combination therapy scenarios. However, elderly patients experienced more AEs with antibody-drug conjugates compared to younger counterparts (56 % vs 14 %, P = 0.036) and were more likely to discontinue treatment due to toxicity (15 % vs 7 %; P = 0.011). No significant age-related differences in response rates and survival outcomes were observed across treatment modalities, except for immunotherapy-based regimens for which elderly patients exhibited higher response rates, disease control rates, and prolonged progression-free survival., Conclusions: Our findings suggest that elderly exhibit comparable safety and efficacy outcomes to younger patients in early-phase clinical trials for new cancer drugs. This underscores the importance of including elderly patients in phase I/II trials to ensure the generalizability of study results and mitigate age-related disparities in cancer treatment access., Competing Interests: Declaration of Competing Interest Disclosures: SM reports expenses reimbursement from Menarini/Stemline and AstraZeneca. PT discloses research funding (to institution) from AstraZeneca and consultancy/advisory role for AstraZeneca, Daiichi Sankyo, Gilead, Novartis and Lilly. MC reports personal fees from Lilly, Sermonix, Data Genomics, Foundation Medicine, Guardant Health, Celcuity, Iylon, and Ellipses and grants and personal fees from Pfizer, AZ and Menarini, all outside the submitted work. CC reports consultancy/advisory role/speaker bureau: AstraZeneca, Daiichi Sankyo, MSD, Gilead, Lilly, Roche, Pfizer, Novartis and Seagen, all outside the submitted work. AM has received honoraria as a consultant, advisor or speaker from Roche and Menarini/Stemline, and has received support for accommodation and travel from AstraZeneca, all outside the submitted work. AE reports speaker bureau: Daiichi Sankyo, Novartis, all outside the submitted work. GC reports payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing or educational events: Lilly, Pfizer, Relay, Gilead, Novartis; Consulting fees: BMS, Roche, Pfizer, Novartis, Lilly, Astra Zeneca, Daichii Sankyo, Merck, Seagen, Ellipsis, Gilead, Menarini; Grants or contracts: Merck; Support for attending meetings and/or travel: Daichii Sankyo. Institutional research funding for conducting Phase 1 and 2 clinical trials: Pfizer, Roche, Novartis, Sanofi, Celgene, Servier, Orion, AstraZeneca, Seattle Genetics, AbbVie, Tesaro, BMS, Merck Serono, Merck Sharp Dohme, Janssen-Cilag, Philogen, Bayer, Medivation, Medimmune. All outside the submitted work. No other potential conflicts of interest are reported., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Baseline tumor size (BTS) has been associated with outcomes in patients with cancer treated with immunotherapy. However, the prognostic impact of BTS on patients receiving targeted therapies (TTs) remains undetermined., Methods: We reviewed data of patients with advanced solid tumors consecutively treated within early-phase clinical trials at our institution from 01/2014 to 04/2021. Treatments were categorized as immunotherapy-based or TT-based (biomarker-matched or not). BTS was calculated as the sum of RECIST1.1 baseline target lesions., Results: A total of 444 patients were eligible; the median BTS was 69 mm (IQR 40-100). OS was significantly longer for patients with BTS lower versus higher than the median (16.6 vs. 8.2 months, P < .001), including among those receiving immunotherapy (12 vs. 7.5 months, P = .005). Among patients receiving TT, lower BTS was associated with longer PFS (4.7 vs. 3.1 months, P = .002) and OS (20.5 vs. 9.9 months, P < .001) as compared to high BTS. However, such association was only significant among patients receiving biomarker-matched TT, with longer PFS (6.2 vs. 3.3 months, P < .001) and OS (21.2 vs. 6.7 months, P < .001) in the low-BTS subgroup, despite a similar ORR (28% vs. 22%, P = .57). BTS was not prognostic among patients receiving unmatched TT, with similar PFS (3.7 vs. 4.4 months, P = .30), OS (19.3 vs. 11.8 months, P = .20), and ORR (33% vs. 28%, P = .78) in the 2 BTS groups. Multivariate analysis confirmed that BTS was independently associated with PFS (P = .03) and OS (P < .001) but not with ORR (P = .11)., Conclusions: Higher BTS is associated with worse survival outcomes among patients receiving biomarker-matched, but not biomarker-unmatched TT., (© The Author(s) 2023. Published by Oxford University Press.)

Purpose: Initial findings in patients with cancer suggest a lower seroconversion to SARS-CoV-2 vaccination possibly related to myelo-immunosuppressive therapies. We conducted a prospective study to assess factors predicting poor seroconversion and adverse events following immunisation (AEFI) to the BNT162b2 vaccine in patients on active treatment., Patients and Methods: Cancer patients, candidates to two doses of BNT162b2 SARS-CoV-2 vaccination, were enrolled. Patients on active surveillance served as controls. The primary endpoint was poor seroconversion (anti S1/S2 IgG < 25 AU/mL) after 21 days from the second dose., Results: Between March and July 2021, 320 subjects were recruited, and 291 were assessable. The lack of seroconversion at 21 days from the second dose was 1.6% (95% CI, 0.4-8.7) on active surveillance, 13.9% (8.2-21.6) on chemotherapy, 11.4% (5.1-21.3) on hormone therapy, 21.7% (7.5-43.7) on targeted therapy and 4.8% (0.12-23.8) on immune-checkpoint-inhibitors (ICI). Compared to controls, the risk of no IgG response was greater for chemotherapy (p = 0.033), targeted therapy (0.005) and hormonotherapy (p = 0.051). Lymphocyte count < 1 × 10 9 /L (p = 0.04) and older age (p = 0.03) also significantly predicted poor seroconversion. Overall, 43 patients (14.8%) complained of AEFI, mostly of mild grade. Risk of AEFI was greater in females (p = 0.001) and younger patients (p = 0.009)., Conclusion: Chemotherapy, targeted therapy, hormone therapy, lymphocyte count < 1 × 10 9 /L, and increasing age predict poor seroconversion after two doses of BNT162b2 in up to 20% of patients, indicating the need for a third dose and long-term serological testing in non-responders. AEFI occur much more frequently in women and younger subjects who may benefit from preventive medications. CLINICALTRIALS., Gov Identifier: NCT04932863., Competing Interests: Conflict of interest statement We declare no competing interests., (Copyright © 2021. Published by Elsevier Ltd.)