Investigator
Hpital Cochin
Platinum free interval and clinical benefit of the second-line chemotherapy in recurrent uterine and ovarian carcinosarcoma: a retrospective cohort analysis
Uterine and ovarian carcinosarcomas (OCSs) are rare and aggressive neoplasms. We assessed whether progression free survival after initial treatment (PFS1) was associated with the clinical benefit of chemotherapy after progression, estimated as overall survival (OS) after progression/relapse. All consecutive patients treated with chemotherapy for stage I-IV uterine/OCS in Cochin University Hospital between 2010 and 2022 were included in this retrospective cohort. Association between PFS1 and OS after progressive disease (PD) was determined by Cox regression. Optimal PFS1 threshold for OS after PD prediction was determined by a time-dependent receiver operating characteristic-curve analysis. Forty patients treated for endometrial (n=32) or OCS (n=8) were included. Median PFS1 and OS after PD were 16 months 95% confidence interval (95% CI=11-not available [NA]) and 6 months (95% CI=2-15). In patients who relapsed/progressed (n=20), OS after PD was anticipated by PFS1 (Pearson r=0.61; area under the curve=0.79; 95% CI=0.6-1). At the threshold of PFS1 ≤/>9 months (n=6/n=7), median OS post PD were 2 months (0.1-NA) and 15 months (6-NA), for patients treated with platinum/anthracycline based chemotherapy in second line. Patients receiving best supportive care alone (n=7) had a median OS post PD of 8 months (1.3-NA). Our results highlight that a subgroup of carcinosarcomas patients exhibits a durable benefit from chemotherapy in the relapse settings, and suggest the use of PFS1, as a proxy of platinum-sensitivity, to select patients who might derive higher clinical benefit of a 2nd line of chemotherapy.
Efficacy of subsequent therapies in patients with advanced ovarian cancer who relapse after first-line olaparib maintenance: results of the PAOLA-1/ENGOT-ov25 trial.
The use of first-line poly(ADP-ribose) polymerase (PARP) inhibitor maintenance therapy is increasing in advanced ovarian cancer. Understanding the efficacy of first subsequent therapy (FST) in patients experiencing disease progression in the first-line setting is important to optimize postprogression treatments. We evaluated the efficacy of FST in patients from PAOLA-1/ENGOT-ov25 (NCT02477644) who received first-line olaparib maintenance. This post hoc analysis evaluated the efficacy of subsequent chemotherapy following disease progression by assessing time from FST to second subsequent therapy (SST) according to whether progression occurred during versus after first-line olaparib maintenance and FST type. A multivariate Cox model was used in the olaparib plus bevacizumab arm to identify prognostic factors influencing the efficacy of subsequent chemotherapy. Of 806 randomized patients, 544 (67.5%) progressed and received subsequent chemotherapy. The median time from FST to SST was shorter in patients in the olaparib plus bevacizumab arm who progressed during first-line olaparib maintenance (6.1 months) than in those who progressed after first-line olaparib maintenance (11.4 months). Multivariate analysis indicated that progression after (versus during) first-line olaparib maintenance influenced time from FST to SST (hazard ratio 0.65, 95% confidence interval 0.50-0.84; P = 0.0011) independently of platinum-free interval or clinical risk. Among patients who progressed and received platinum-based chemotherapy with a PARP inhibitor as FST, the efficacy of subsequent therapies was also dependent on whether progression occurred during versus after first-line olaparib maintenance. These results suggest that the timing of disease progression relative to first-line olaparib maintenance may impact the efficacy of subsequent platinum-based chemotherapy. Although results should be interpreted with caution, across all subgroups, including patients who received platinum-based chemotherapy with PARP inhibitor rechallenge as FST, the median time from FST to SST was longer if progression occurred after versus during first-line olaparib maintenance.
