Efficacy Of Subsequent Chemotherapy Research Articles

Efficacy of subsequent therapies in patients (pts) with advanced ovarian cancer (AOC) in the phase III PAOLA-1/ENGOT-ov25 trial according to whether disease progression occurred during or after the end of olaparib (ola) maintenance.

5550 Background: In the PAOLA-1/ENGOT-ov25 trial (NCT02477644), maintenance ola (a PARP inhibitor) + bevacizumab (bev) led to prolonged progression-free and overall survival vs placebo (pbo) + bev in AOC pts, specifically those with homologous recombination-deficient (HRD+) tumors (Ray-Coquard et al. ESMO 2022, LBA29). Here, we explore the efficacy of subsequent chemotherapy (CT) in pts after progression on first-line (1L) treatment in PAOLA-1. Methods: The efficacy of subsequent CT was explored by analyzing the median time from first subsequent therapy (FST) to second subsequent therapy (SST). Efficacy was compared by FST type, HRD status, and timing of progression (during/after ola). A multivariate Cox model was used in ola + bev pts to identify prognostic factors influencing time from FST to SST, including HRD status, platinum-free interval (PFI), clinical risk based on disease stage and surgical status, timing of progression, and response to 1L CT. All P values are exploratory. Results: In total, 544/806 (67.5%) pts progressed and received subsequent CT: 338/537 (62.9%) ola + bev pts and 206/269 (76.6%) pbo + bev pts. In the overall population and in the subgroup who received platinum-based combination therapy (PBC), time from FST to SST was shortest in pts who progressed during ola (Table). Pts who progressed after ola had similar outcomes to pbo + bev pts (Table). Efficacy was broadly consistent regardless of HRD status (Table). The multivariate analysis confirmed that progression after (vs during) ola prolonged time from FST to SST (hazard ratio [HR] 0.65, 95% confidence interval [CI] 0.50–0.84; P=0.0011) independently of other known prognostic factors, such as PFI ≥12 vs <12 months (HR 0.38, 95% CI 0.29–0.51; P<0.0001) or lower vs higher clinical risk (0.58, 0.42–0.81; P=0.0015). Conclusions: In this post hoc exploratory analysis of PAOLA-1, the efficacy of subsequent CT at relapse appeared dependent on whether progression occurred during or after the end of ola treatment. Efficacy was reduced when relapse occurred during ola but was comparable between pts who progressed after ola vs pbo + bev pts. Clinical trial information: NCT02477644 . [Table: see text]

Phase Ib dose-escalation study of the hypoxia-modifier myo-inositol trispyrophosphate in patients with hepatopancreatobiliary tumors

Abstract Objective Hypoxia is present in most solid tumors and acts as a driver of malignancy. Myo-inositol trispyrophosphate (ITPP) is a novel re-oxygenating compound without apparent toxicity. In preclinical models, it potentiates the efficacy of subsequent chemotherapy through vascular normalization. We sought to assess the safety, tolerability, and preliminary efficacy of ITPP. Methods In this monocentric, open-label, dose-escalation study following a 3+3 design, eligible patients with advanced primary and secondary hepatopancreatobiliary tumors received nine 8-h infusions of ITPP during 3 weeks across eight dose levels (1866–14,500 mg/m2/dose), followed by standard chemotherapy. Primary endpoints were safety and tolerability. Secondary endpoints were pharmacokinetics and estimation of efficacy based on radiological responses and angiogenic serum markers. Registration number: NCT02528526. Results From April 2015 to July 2018, a total of 28 enrolled patients were assessed for the primary endpoints. ITPP was safe up to single doses of 12,390 mg/m2, and 32 ITPP-related adverse events occurred: 19 (67.8%) hypercalcemia, 5 (17.8%) hyponatremia, and 4 (14.2%) hypomagnesemia. Following ITPP monotherapy, 52% of patients displayed morphological disease stabilization. Following subsequent chemotherapy, 10% showed a partial response, and 60% had stable disease. Angiogenic markers were decreased in 60% after ITPP and tended to correlate with responses and survival after chemotherapy. Conclusion Administration of ITPP is safe up to 12,390 mg/m2 with favorable pharmacokinetics. Preliminary translational efficacy data show decreased angiogenic markers, which might indicate an anti-hypoxic effect and enhancement of chemotherapy through ITPP.

Efficacy of platinum agents for stage III non-small-cell lung cancer following platinum-based chemoradiotherapy: a retrospective study

BackgroundPlatinum-based chemoradiotherapy is the standard treatment for unresectable stage III non-small-cell lung cancer (NSCLC). However, few studies have evaluated the efficacy of subsequent chemotherapy for relapsed NSCLC following platinum-based chemoradiotherapy. This study aimed to evaluate the efficacy of platinum-doublet chemotherapy as a second-line treatment for patients with unresectable stage III NSCLC.MethodsWe retrospectively evaluated patients with unresectable stage III NSCLC treated with cytotoxic chemotherapy following platinum-based chemoradiotherapy who were registered in a nationwide registry NSCLC database. Patients were divided into the platinum-doublet chemotherapy (platinum) group and single-agent chemotherapy (non-platinum) group based on the type of second-line chemotherapy.ResultsThe platinum group (n = 119) showed significantly better overall survival (OS) than the non-platinum group (n = 201) (median OS: 21.5 vs. 10.5 months, hazard ratio [HR]: 0.54, 95% confidence interval [CI]: 0.40–0.73, p < 0.001). OS from the beginning of chemoradiotherapy was also significantly better in the platinum group than in the non-platinum group (median OS: 34.9 vs. 21.8 months, HR: 0.58, 95% CI: 0.43–0.79, p = 0.001). In the multivariate analysis, platinum-doublet chemotherapy as second-line therapy, female sex, clinical stage IIIA, and duration of ≥ 8.6 months from the beginning of first-line therapy to the beginning of second-line therapy were associated with significantly better OS.ConclusionPlatinum-doublet chemotherapy as a second-line therapy may prolong survival in unresectable stage III NSCLC patients following platinum-based chemoradiotherapy. Thus, re-administration of platinum agents may be a promising treatment for unresectable stage III NSCLC treated with platinum-based chemoradiotherapy.

P1-180 - The efficacy of subsequent chemotherapy after programmed cell death 1 inhibitor treatment in non-small cell lung cancer

P1-180 - The efficacy of subsequent chemotherapy after programmed cell death 1 inhibitor treatment in non-small cell lung cancer

Responses to chemotherapy in patients with metastatic urothelial cancer (MUC) after frontline immunotherapy.

e16004 Background: The effect of prior immune checkpoint inhibition therapy (CI) on the efficacy of subsequent chemotherapy is largely unknown in MUC. The identification of the optimal sequence of chemotherapy and IO is yet to be determined, but may influence outcomes. Methods: A retrospective audit and comparison of patients who progressed after first and second line CI and received subsequent standard chemotherapy was performed. Date was collected across a broad spectrum of CI. We report on patient’s characteristics and response rates of 28 sequential patients collected from two institutions who received chemotherapy after CI. Patients were separated into 2 cohorts. Cohort A had not previously received chemotherapy (n = 14), cohort B had previously received at least 1 chemotherapy regimen (n = 14). Central radiology review was performed. We assessed objective response rate by RECIST v 1.1. Kaplan Meier method was used. Results: Median age for the whole cohort was 64 yrs (45-80). ECOG was 0/1 in 89,3% and 2 in 10,7% at the time of starting chemotherapy. The commonest chemotherapy regimen in cohort A and B were carboplatin-gemcitabine (71%) and carboplatin paclitaxel (50%) respectively. 75% of the patients were intermediate risk group. In Cohort A 63% responded to chemotherapy whereas in cohort B only 3 patients showed response. The median change in target lesions in the front line immunotherapy cohort was -60% (-81 to +1%). Both patients who responded to 2nd line chemotherapy after CI had a long interval between first and 2nd line chemotherapy (9-24 months). Conclusions: Chemotherapy maintains its efficacy after front line CI with deep responses. Although numbers are modest, results strongly suggest patients should be offered chemotherapy in this setting.

High responses to chemotherapy in patients with metastatic urothelial cancer (MUC) after frontline immunotherapy.

377 Background: The effect of prior immune checkpoint inhibition therapy (CI) on the efficacy of subsequent chemotherapy is largely unknown in MUB. The identification of the optimal sequence of chemotherapy and IO is yet to be determined, but may influence outcomes. Methods: A retrospective audit and comparison of patients who progressed after first and second line CI and received subsequent standard chemotherapy was performed. Date was collected across a broad spectrum of CI. We report on patient’s characteristics and response rates of 20 sequential patients collected from one institution who received chemotherapy after CI. Patients were separated into 2 groups. Group A had not previously received chemotherapy (n=10), group B had previously received at least 1 chemotherapy regimen (n=10). Central radiology review was performed. We assessed objective response rate by RECIST v 1.1. Kaplan Meier method was used. Results: Median age for the whole cohort was 64 yrs (45-80). The commonest chemotherapy regimen in group A and B were cisplatin-gemcitabine (80%) and carboplatin paclitaxel (70%) respectively. Results are summarised in the table. The median change in target lesions in the front line immunotherapy cohort was -49% (-81 to +8%). Only two patients (20%) in group B responded to chemotherapy and both presented a long interval between first and 2ndline chemotherapy (9-12 months); compared to 56% responding in group A. Conclusions: Chemotherapy maintains its efficacy after front line CI with deep responses. Although numbers are modest, results strongly suggest patients should be offered chemotherapy in this setting. [Table: see text]