Prior Lines Of Chemotherapy Research Articles

EUS-FNA Biopsies to Guide Precision Medicine in Pancreatic Cancer: Results of a Pilot Study to Identify KRAS Wild-Type Tumours for Targeted Therapy.

BackgroundPancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer death and lacks effective treatment options. Diagnostic endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) biopsies represent an appealing source of material for molecular analysis to inform targeted therapy, as they are often the only available tissue for patients presenting with PDAC irrespective of disease stage. However, EUS-FNA biopsies are typically not used to screen for precision medicine studies due to concerns about low tissue yield and quality. Epidermal growth factor receptor (EGFR) inhibition has shown promise in clinical trials of unselected patients with advanced pancreatic cancer, but has not been prospectively tested in KRAS wild-type patients. Here, we examine the clinical utility of EUS-FNA biopsies for molecular screening of KRAS wild-type PDAC patients for targeted anti-EGFR therapy to assess the feasibility of this approach.Patients and MethodsFresh frozen EUS-FNA or surgical biopsies from PDAC patient tumours were used to screen for KRAS mutations. Eligible patients with recurrent, locally advanced, or metastatic KRAS wild-type status who had received at least one prior line of chemotherapy were enrolled in a pilot study (ACTRN12617000540314) and treated with panitumumab at 6mg/kg intravenously every 2 weeks until progression or unacceptable toxicity. The primary endpoint was 4-month progression-free survival (PFS).Results275 patient biopsies were screened for KRAS mutations, which were detected in 88.3% of patient samples. 8 eligible KRAS wild-type patients were enrolled onto the interventional study between November 2017 and December 2020 and treated with panitumumab. 4-month PFS was 14.3% with no objective tumour responses observed. The only grade 3/4 treatment related toxicity observed was hypomagnesaemia.ConclusionsThis study demonstrates proof-of-principle feasibility to molecularly screen patients with pancreatic cancer for targeted therapies, and confirms diagnostic EUS-FNA biopsies as a reliable source of tumour material for molecular analysis. Single agent panitumumab was safe and tolerable but led to no objective tumour responses in this population.

Phase II study of enzalutamide in androgen receptor positive, recurrent, high- and low-grade serous ovarian cancer

ObjectivesWe sought to determine the safety and efficacy of the oral androgen receptor antagonist enzalutamide in patients with previously treated, recurrent, AR-positive (AR+) ovarian cancer. MethodsThis was a single-institution phase II study of patients with AR+ ovarian cancer with measurable disease with 1–3 prior lines of chemotherapy; patients were screened for enrollment from 11/2013–7/2018. Following consent, archival tissue was evaluated for AR+. Enrolled patients received daily enzalutamide 160 mg until progression of disease or treatment discontinuation. Adverse events were graded by CTCAE v4.0. Co-primary endpoints were 6-month progression-free survival (PFS6) and overall response rate (ORR) by RECIST 1.1 criteria. ResultsDuring the study period, 160 patients were screened and 59 (45 high-grade serous [HGS] and 14 low-grade serous [LGS]) consented to treatment on study. There was 1 confirmed and 1 unconfirmed partial response. The ORR was 1.7% (90% CI: 0.2–100%). The overall PFS6 rate (as binary) was 22% (90% CI: 15.1–100%). The 6-month PFS rate (as time to event) was 19.8% for HGS patients (90% CI: 12.7–100%) and 38.5% (90% CI: 21.7%–100%) for LGS patients. Grade 3 toxicities occurred in 6 patients (one toxicity (Grade 3 rash) was considered a dose-limiting toxicity). One patient died of cardiac arrest after 42 days on treatment of a cardiac arrest not attributed to study drug. ConclusionsThe study met its primary endpoint, with a PFS6 rate of 22% (n = 13); however, the overall response rate was low. Enzalutamide was well tolerated and may be a potential treatment option in select patients.

Prophylactic Corticosteroid Use with Axicabtagene Ciloleucel (Axi-Cel) in Patients (Pts) with Relapsed/Refractory Large B-Cell Lymphoma (R/R LBCL): One-Year Follow-up of ZUMA-1 Cohort 6 (C6)

Prophylactic Corticosteroid Use with Axicabtagene Ciloleucel (Axi-Cel) in Patients (Pts) with Relapsed/Refractory Large B-Cell Lymphoma (R/R LBCL): One-Year Follow-up of ZUMA-1 Cohort 6 (C6)

Nanoliposomal irinotecan plus fluorouracil and folinic acid as a second-line treatment option in patients with metastatic pancreatic ductal adenocarcinoma: a retrospective cohort study

BackgroundAccording to the NAPOLI-1 trial, nanoliposomal irinotecan (nal-IRI) plus fluorouracil/folinic acid (5-FU/LV) showed improved overall survival compared to fluorouracil alone for patients with metastatic pancreatic cancer who were previously treated with gemcitabine-based therapy. In that trial, Asian patients had frequent dose modification due to haematological toxicity. There has been limited information on the clinical benefits and toxicity of this regimen in real-world settings. In this study, we assessed real-world experience of nal-IRI plus 5-FU/LV in patients with advanced pancreatic cancer after gemcitabine failure.MethodsWe conducted a single institution, retrospective analysis of response, survival and safety in patients who had been treated with nal-IRI with 5-FU/LV. Patients with metastatic pancreatic ductal adenocarcinoma previously treated with gemcitabine-based therapy received nal-IRI (80 mg/m2) with 5-FU/LV every 2 weeks. Kaplan-Meier analysis was performed to obtain median progression free survival and median overall survival. The hazard ratio and 95% confidence interval (CI) were estimated using a stratified Cox regression model. A multivariate Cox proportional hazards regression model was used to identify the effects of clinical factors.ResultsFifty-one patients received nal-IRI plus 5-FU/LV between January 2015 and December 2020. The median age was 67 years, and males were 58.8%. A total of 40 (78.4%) and 11 (21.6%) patients had received one and two lines of prior chemotherapy before enrollment, respectively. Median progression-free survival was 2.8 months (95% CI 1.8–3.7) and median overall survival was 7.0 months (95% CI 6.0–7.9). Chemotherapy doses were reduced or delayed in 33 (64.7%) patients during the first 6 weeks and median relative dose intensity was 0.87. Thirty-six (70.6%) patients experienced grade 3 or 4 adverse events, most commonly neutropenia (58.8%). Most non-haematologic adverse events were under grade 2. Since the start of first-line chemotherapy, median overall survival was 16.3 months (95% CI 14.1–18.4).ConclusionsNal-IRI plus 5-FU/LV seems to be effective, with manageable toxicities, following gemcitabine-based treatment in patients with metastatic pancreatic ductal adenocarcinoma. Nal-IRI plus 5-FU/LV following gemcitabine with nab-paclitaxel is a feasible sequential treatment option in patients with metastatic pancreatic cancer.Trial registrationRetrospectively registered.

Avelumab in patients with previously treated metastatic Merkel cell carcinoma (JAVELIN Merkel 200): updated overall survival data after >5 years of follow-up

BackgroundMerkel cell carcinoma (MCC) is a rare, aggressive skin cancer that has a poor prognosis in patients with advanced disease. Avelumab [anti-programmed death-ligand 1 (PD-L1)] became the first approved treatment for patients with metastatic MCC (mMCC), based on efficacy and safety data observed in the JAVELIN Merkel 200 trial. We report long-term overall survival (OS) data after >5 years of follow-up from the cohort of patients with mMCC whose disease had progressed after one or more prior lines of chemotherapy.Patients and methodsIn Part A of the single-arm, open-label, phase II JAVELIN Merkel 200 trial, patients with mMCC that had progressed following one or more prior lines of chemotherapy received avelumab 10 mg/kg by intravenous infusion every 2 weeks until confirmed disease progression, unacceptable toxicity, or withdrawal. In this analysis, long-term OS was analyzed.ResultsIn total, 88 patients were treated with avelumab. At data cut-off (25 September 2020), median follow-up was 65.1 months (range 60.8-74.1 months). One patient (1.1%) remained on treatment, and an additional patient (1.1%) had reinitiated avelumab after previously discontinuing treatment. Median OS was 12.6 months [95% confidence interval (CI) 7.5-17.1 months], with a 5-year OS rate of 26% (95% CI 17% to 36%). In patients with PD-L1+ versus PD-L1− tumors, median OS was 12.9 months (95% CI 8.7-29.6 months) versus 7.3 months (95% CI 3.4-14.0 months), and the 5-year OS rate was 28% (95% CI 17% to 40%) versus 19% (95% CI 5% to 40%), respectively (HR 0.67; 95% CI 0.36-1.25).ConclusionAvelumab monotherapy resulted in meaningful long-term OS in patients with mMCC whose disease had progressed following chemotherapy. These results further support the role of avelumab as a standard of care for patients with mMCC.

Longitudinal Trends in Palliative Radiotherapy, Specialty Palliative Care, and Symptoms Over Time Among Patients With Metastatic Cancer

The purpose of this study is to examine longitudinal trends in palliative radiotherapy (RT) and specialty palliative care (PC) among patients with metastatic cancer, determine predictors of earlier PC utilization, and explore distributions of PC symptoms over time. We hypothesize that most palliative RT and specialty PC visits occurred in the last 25% of life remaining from time of diagnosis of metastatic cancer to death.We retrospectively reviewed 162 patients with metastatic cancer who received palliative RT at our institution between 7/2017 and 2/2018; 74 of these patients received specialty PC. Descriptive statistics summarized frequencies of palliative RT consultations, PC visits, and symptoms experienced over time (quartiles 1-3: first 75% vs quartile 4: last 25% of life remaining from metastatic diagnosis to death). We used logistic regression analyses to determine predictors of receiving earlier specialty PC (quartiles 1-3) and Fisher's exact test to examine differences in incidences of hospice referral for earlier (quartiles 1-3) vs later PC (quartile 4).At the time of diagnosis of metastatic cancer, median overall survival among patients receiving specialty PC was 7.0 months (IQR: 4.2-11.6), with the last 25% of life representing a median of 1.75 months. There were 16.2%, 14.9%, 25.5%, and 43.5% of all palliative RT consultations, compared to 9.0%, 11.7%, 16.5%, and 63.8% of all PC visits that occurred in quartiles 1, 2, 3, and 4, respectively. Among the 642 specialty PC visits that occurred, pain was addressed more frequently in quartiles 1-3 (217/559, 38.8%) vs quartile 4 (327/1165, 28.1%), while goals of care and end-of-life symptom management were addressed more frequently in quartile 4 (137/1165, 11.8%) vs quartiles 1-3 (11/559, 2.0%). On multivariable analysis, pain as a presenting PC symptom was a significant independent predictor of receiving earlier PC (OR = 6.41 [95% CI 1.61-34.03], P = 0.015), while patients with receipt of ≥2 prior lines of palliative chemotherapy were less likely to receive earlier PC (OR = 0.20 [95% CI 0.06-0.64], P = 0.009). In a separate regression analysis, both of these variables remained statistically significant after controlling for demographics. There was no statistically significant difference between incidence of hospice referral for those receiving their first specialty PC visit in quartiles 1-3 vs quartile 4 (P = 0.59).Nearly 44% of palliative RT visits compared with 64% of specialty PC visits occurred in the last 25% of life from metastatic diagnosis to death. Patients who reported experiencing pain and those who received ≤1 prior lines of palliative chemotherapy were more likely to have received earlier specialty PC. Identifying factors or symptom triggers that prompt addressing patients' PC needs sooner than the last 2 months of life is needed.

Doxorubicin plus lurbinectedin in patients with advanced endometrial cancer: results from an expanded phase I study

ObjectiveSecond-line treatment of endometrial cancer is an unmet medical need. We conducted a phase I study evaluating lurbinectedin and doxorubicin intravenously every 3 weeks in patients with solid tumors. The...

P45.08 Lorlatinib for Previously Treated ALK-Positive Advanced NSCLC: Primary Efficacy and Safety Data from a Phase 2 Study in China

Lorlatinib, a third-generation inhibitor of anaplastic lymphoma kinase (ALK), was shown in a global Phase 2 study to have potent overall and intracranial (IC) anti-tumor activity in patients with ALK-positive advanced non-small cell lung cancer (NSCLC) after progression on first- and/or second-generation ALK inhibitors (NCT01970865). Here we report primary data from a multicenter Phase 2 study conducted in China that investigated lorlatinib in ALK inhibitor-treated patients with ALK-positive NSCLC (NCT03909971). This ongoing, open-label, Phase 2 study enrolled patients in China with ALK-positive locally advanced/metastatic NSCLC and disease progression after crizotinib as the only ALK-inhibitor (Cohort 1), or after one ALK-inhibitor other than crizotinib, with or without prior crizotinib (Cohort 2). Patients with CNS metastases were eligible to enroll; one prior line of chemotherapy was permitted. All patients received lorlatinib 100 mg QD in a continuous 3-week cycle. The primary endpoint was objective response rate (ORR) by independent central review (ICR) per RECIST v1.1 in Cohort 1. Secondary endpoints included ORR in Cohort 2, IC-ORR, PFS, overall survival (OS), and safety. In total, 109 patients were enrolled: 67 to Cohort 1 and 42 to Cohort 2. Among these, 36 patients in Cohort 1 and 21 patients in Cohort 2 had ≥1 intracranial lesion at baseline per ICR assessment. At data cutoff (August 10, 2020), ORR (95% CI) by ICR in Cohort 1 was 70.1% (57.7–80.7) and in Cohort 2 was 47.6% (32.0–63.6). IC-ORR was 80.6% in Cohort 1 and 47.6% in Cohort 2. See Table for additional response data. Median DOR by ICR was not reached in Cohort 1, and was 11.2 months in Cohort 2. Median PFS by ICR was not reached in Cohort 1, and was 5.6 months in Cohort 2. OS data were immature and median OS was not estimatable in either cohort. Median treatment duration was 11.4 months in Cohort 1 and 8.4 months in Cohort 2. Grades 3–4 treatment-related adverse events (TRAEs) occurred in 36 (53.7%) patients in Cohort 1 and 17 (40.5%) patients in Cohort 2; serious TRAEs occurred in 4 (6.0%) and 5 (11.6 %) patients in each cohort, respectively. No Grade 5 TRAE were reported in either cohort. The most commonly-reported any-grade AEs overall were hypercholesterolemia (92.7%) and hypertriglyceridemia (91.7%).Table 1Summary of response dataCohort 1Cohort 2TotalBest overall response by ICRPatients in analysisN=67N=42N=109ORR, n (%)47 (70.1)20 (47.6)67 (61.5)95% CI57.7–80.732.0–63.651.7–70.6CR8 (11.9)2 (4.8)10 (9.2)PR39 (58.2)18 (42.9)57 (52.3)SD8 (11.9)6 (14.3)14 (12.8)Best overall intracranial response in patients with any intracranial lesionsPatients in analysisN=36N=21N=57IC-ORR, n (%)29 (80.6)10 (47.6)39 (68.4)95% CI64.0–91.825.7–70.254.8–80.1CR19 (52.8)6 (28.6)25 (43.9)PR10 (27.8)4 (19.0)14 (24.6)SD02 (9.5)2 (3.5)CI, confidence interval; CR, complete response; IC, intracranial; ICR, independent central review; ORR, objective response rate; PR, partial response; SD, stable disease Open table in a new tab CI, confidence interval; CR, complete response; IC, intracranial; ICR, independent central review; ORR, objective response rate; PR, partial response; SD, stable disease Lorlatinib showed robust clinical activity in Chinese patients with previously treated ALK-positive NSCLC, including those with CNS metastases. Safety data were consistent with previous findings.

Tumor growth rate during re-challenge chemotherapy with previously used agents as salvage treatment for metastatic colorectal cancer: A retrospective study.

BackgroundIn clinical practice, the same chemotherapeutic agents are occasionally reused (re-challenge) after failure of all available standard chemotherapy options for metastatic colorectal cancer (mCRC). However, the benefits of re-challenge chemotherapy (Re-Cx) are unclear. This retrospective study evaluated the efficacy of Re-Cx, focusing on the tumor growth rate (TGR).MethodsThe study included mCRC patients with measurable lesions who received Re-Cx from November 2011 to October 2018 at National Cancer Center Hospital. Re-Cx was defined as re-administration of agents which had been used in prior lines of chemotherapy and discontinued due to disease progression. We compared the TGR immediately after initiating Re-Cx regimens with that observed at the time of disease progression during prior chemotherapy (Prior-Cx) immediately before Re-Cx.ResultsOf the 25 patients who received Re-Cx, five patients received two Re-Cx regimens. Therefore, a total of 30 cases of Re-Cx were analyzed in this study. The regimens of Re-Cx were oxaliplatin based (19 cases), irinotecan based (8 cases), and others (3 cases). Although the objective response rate to Re-Cx was 0%, the disease control rate was 60% (18 cases), and 40% (12 cases) showed some tumor shrinkage. We compared the effects of Re-Cx and Prior-Cx by the TGR and found that the TGR of Re-Cx was slower than that recorded in Prior-Cx in 26 of 30 cases (87%). In particular, the ratio of% TGR <0, which indicates tumor shrinkage, was obtained in 13 of 30 cases (43.3%). The median progression-free survival and overall survival after Re-Cx were 3.8 and 6.57 months, respectively.ConclusionWe found that Re-Cx may have some anti-tumor efficacy as salvage treatment for mCRC and these results also suggested the clinical benefits of Re-Cx.

Pyrotinib combined with thalidomide in advanced non-small-cell lung cancer patients harboring HER2 exon 20 insertions (PRIDE): protocol of an open-label, single-arm phase II trial

BackgroundStandard therapy for human epidermal growth factor receptor 2 (HER2)-mutant non-small-cell lung cancer (NSCLC) is lacking. The clinical benefits with pan-HER inhibitors (afatinib, neratinib, and dacomitinib), anti-HER2 antibody drug conjugate (ADC) trastuzumab emtansine, and an emerging irreversible tyrosine kinase inhibitor (TKI) poziotinib were modest. Another new ADC trastuzumab deruxtecan showed encouraging outcomes, but only phase I study was completed. Pyrotinib, another emerging irreversible epidermal growth factor receptor (EGFR)/HER2 dual TKI, has been approved in HER2-positive breast cancer in 2018 in China. It has shown promising antitumor activity against HER2-mutant NSCLC in phase II trials, but pyrotinib-related diarrhea remains an issue. The antiangiogenic and immunomodulatory drug thalidomide is a cereblon-based molecular glue that can induce the degradation of the IKAROS family transcription factors IKZF1 and IKZF3. The use of thalidomide can also decrease gastrointestinal toxicity induced by anti-cancer therapy.MethodsThis is an open-label, single-arm phase II trial. A total of 39 advanced NSCLC patients with HER2 exon 20 insertions and ≤ 2 lines of prior chemotherapy will be recruited, including treatment-naïve patients who refuse chemotherapy. Patients are allowed to have prior therapy with immune checkpoint inhibitors and/or antiangiogenic agents. Those who have prior HER2-targeting therapy or other gene alterations with available targeted drugs are excluded. Eligible patients will receive oral pyrotinib 400 mg once daily and oral thalidomide 200 mg once daily until disease progression or intolerable toxicity. The primary endpoint is objective response rate.DiscussionThe addition of thalidomide to pyrotinib is expected to increase the clinical benefit in advanced NSCLC patients with HER2 exon 20 insertions, and reduce the incidence of pyrotinib-related diarrhea. We believe thalidomide is the stone that can hit two birds.Trial registrationClinicalTrials.gov Identifier: NCT04382300. Registered on May 11, 2020.

Lurbinectedin versus pegylated liposomal doxorubicin or topotecan in patients with platinum-resistant ovarian cancer: A multicenter, randomized, controlled, open-label phase 3 study (CORAIL)

ObjectiveThe randomized phase 3 CORAIL trial evaluated whether lurbinectedin improved progression-free survival (PFS) compared to pegylated liposomal doxorubicin (PLD) or topotecan in patients with platinum-resistant ovarian cancer. MethodsPatients were randomly assigned (1:1) to lurbinectedin 3.2 mg/m2 1-h i.v. infusion q3wk (experimental arm), versus PLD 50 mg/m2 1-h i.v. infusion q4wk or topotecan 1.50 mg/m2 30-min i.v. infusion Days 1–5 q3wk (control arm). Stratification factors were PS (0 vs. ≥1), prior PFI (1–3 months vs. >3 months), and prior chemotherapy lines (1–2 vs. 3). The primary endpoint was PFS by Independent Review Committee in all randomized patients. This study was registered with ClinicalTrials.gov, NCT02421588. Results442 patients were randomized: 221 in lurbinectedin arm and 221 in control arm (127 PLD and 94 topotecan). With a median follow-up of 25.6 months, median PFS was 3.5 months (95% CI, 2.1–3.7) in the lurbinectedin arm and 3.6 months (95% CI, 2.7–3.8) in the control arm (stratified log-rank p = 0.6294; HR = 1.057). Grade ≥ 3 treatment-related adverse events (AEs) were most frequent in the control arm: 64.8% vs. 47.9% (p = 0.0005), mainly due to hematological toxicities. The most common grade ≥ 3 AEs were: fatigue (7.3% of patients) and nausea (5.9%) with lurbinectedin; mucosal inflammation (8.5%) and fatigue (8.0%) in the control arm. ConclusionsThe primary endpoint of improvement in PFS was not met. Lurbinectedin showed similar antitumor efficacy and was better tolerated than current standard of care in patients with platinum-resistant ovarian cancer.

Full population results from the core phase of CompLEEment-1, a phase 3b study of ribociclib plus letrozole as first-line therapy for advanced breast cancer in an expanded population

PurposeCompLEEment-1 is a phase 3b trial in an expanded patient population with hormone receptor-positive (HR +), human epidermal growth factor receptor-2–negative (HER2–) advanced breast cancer (ABC), the largest current trial of cyclin-dependent kinase 4 and 6 inhibitors in ABC.MethodsPatients treated with ≤ 1 line of prior chemotherapy and no prior endocrine therapy for ABC received ribociclib 600 mg/day (3-weeks-on/1-week-off) plus letrozole 2.5 mg/day and additionally monthly goserelin/leuprolide in men and pre-/perimenopausal women. Eligibility criteria allowed inclusion of patients with stable CNS metastases and an Eastern Cooperative Oncology Group performance status of 2. Primary objectives were safety and tolerability, and secondary objectives were efficacy and quality of life (QoL).ResultsOverall, 3,246 patients were evaluated (median follow-up 25.4 months). Rates of all-grade and grade ≥ 3 treatment-related adverse events (AEs) were 95.2% and 67.5%, respectively. Treatment-related discontinuations due to all grade and grade ≥ 3 AEs occurred in 12.9% and 7.3% of patients, respectively. Rates of all-grade AEs of special interest (AESI) were as follows: neutropenia (74.5%), increased alanine aminotransferase (16.2%), increased aspartate aminotransferase (14.1%), and QTcF prolongation (6.7%); corresponding values for grade ≥ 3 AESI were 57.2%, 7.7%, 5.7%, and 1.0%, respectively. Median time to progression was 27.1 months (95% confidence interval, 25.7 to not reached). Patient QoL was maintained during treatment.ConclusionSafety and efficacy data in this expanded population were consistent with the MONALEESA-2 and MONALEESA-7 trials and support the use of ribociclib plus letrozole in the first-line setting for patients with HR + , HER2– ABC.Trial registrationlinicalTrials.gov NCT02941926.

A Real-world Efficacy of Nab-paclitaxel Monotherapy in Metastatic Breast Cancer.

PurposeWe aimed to assess the real-world efficacy of nab-paclitaxel in metastatic breast cancer patients.Materials and MethodsThis is a retrospective study performed in two tertiary referral hospitals in Korea. Patients with metastatic breast cancer treated with nab-paclitaxel (Abraxane) between March 2016 and March 2020 were enrolled.ResultsA total of 102 patients with metastatic breast cancer were included. Patients were heavily pre-treated with a median of four prior lines of chemotherapy (5 lines when including endocrine therapy in hormone-receptor-positive patients), and 66 patients (64.7%) were exposed to taxanes in the metastatic setting. According to St. Gallen molecular subtypes, 36 patients (35.3%) were luminal A, 28 (27.5%) were luminal B, 18 (17.7%) were human epidermal growth factor receptor 2–positive and 20 (19.6%) had triple-negative disease. Fifty patients (49.0%) were treated with a 3-weekly regimen (260 mg/m2 on day 1 every 3 weeks), and 52 (51.0%) were treated with a weekly regimen (100 mg/m2 every week). Objective response rate was 22.9%. After a median follow-up of 22.0 months, median progression-free survival (PFS) was 4.0 months (95% confidence interval [CI], 2.6 to 4.8) and median overall survival was 8.7 months (95% CI, 7.5 to 11.2). Patients treated with weekly regimen had longer PFS compared to 3-weekly regimen (5.5 vs. 2.3 months, p < 0.001). Multivariate analysis revealed the treatment regimen as an independent prognostic factor for PFS. There was no grade 3 or 4 hypersensitivity reaction.ConclusionThis real-world data shows that nab-paclitaxel is a reasonable treatment option in heavily pre-treated and/or taxane-exposed metastatic breast cancer patients.

Olaparib treatment in patients with platinum-sensitive relapsed ovarian cancer by BRCA mutation and homologous recombination deficiency status: secondary efficacy results from the phase II LIGHT study

<h3>Objectives:</h3> LIGHT (NCT02983799) evaluated olaparib treatment in patients with platinum-sensitive relapsed (PSR) ovarian cancer by <i>BRCA</i> mutation (<i>BRCA</i>m) and homologous recombination repair deficiency (HRD) status; the primary analysis demonstrated objective response rates (ORRs) of 69%, 64%, 29%, and 10% in cohorts of patients with a germline (g) <i>BRCA</i>m, with tumors with somatic (s) <i>BRCA</i>m, HRD-positive (non<i>-BRCA</i>m), and HRD-negative status, respectively (Cadoo K <i>et al.</i> ASCO 2020). Here, we report pre-specified secondary efficacy endpoints and subgroup analyses. <h3>Methods:</h3> In this open-label, non-randomized study, patients with PSR ovarian cancer and ≥1 prior line of platinum-based chemotherapy received olaparib monotherapy (300 mg bid). Patients were assigned to one of four cohorts based on whether they had a g<i>BRCA</i>m, tumors with s<i>BRCA</i>m, had HRD-positive (non<i>-BRCA</i>m) tumors, or HRD-negative tumors. Testing for g<i>BRCA</i>m was completed using Myriad BRACAnalysis CDx; s<i>BRCA</i>m testing was done with Myriad myChoice CDx. Genomic instability (GI) was assessed using the Myriad myChoice HRD test; tumors were deemed HRD-positive if they had a GI score ≥42. Secondary efficacy endpoints included investigator-assessed progression-free survival (PFS; RECIST v1.1) and cancer antigen (CA)-125 response. Time to any progression (TTAP) was calculated from the date of the first dose of olaparib until the earliest date of RECIST v1.1 or CA-125 disease progression, or death. <h3>Results:</h3> The analysis was timed ~6 months after the last patient was enrolled (data cut-off, Aug 27, 2019). Of 271 enrolled patients who had received olaparib, 270 had measurable disease at baseline and were included in efficacy analyses (13 patients whose Myriad test result was failed or missing could not be assigned to a cohort; efficacy in these patients was analyzed separately). ORR and PFS by prior line of chemotherapy, CA-125 response, and TTAP are summarized in the Table. ORRs ~60-70% were observed in the gBRCAm and sBRCAm cohorts and ~30% in the HRD-positive (non-BRCAm) cohort, both in patients with 1 or ≥2 prior lines of chemotherapy. Similarly, median PFS in patients was ~10-11 months in the <i>BRCA</i>m cohorts, and ~5-7 months in the HRD-positive (non<i>-BRCA</i>m) cohort, both in patients with 1 or ≥2 prior lines of chemotherapy. In the <i>BRCA</i>m cohorts, a high proportion of patients achieved a CA-125 response and complete response (CR), with a CA-125 CR rate of 60% and 68% in the <i>BRCA</i>m cohorts and 29% in the HRD-positive non<i>-BRCA</i>m cohort. Median TTAP was ~11 months in the <i>BRCA</i>m cohorts, and 7.2 months in the HRD-positive (non<i>-BRCA</i>m) cohort. <h3>Conclusions:</h3> Secondary efficacy data and subgroup analyses from the LIGHT study of olaparib monotherapy as treatment for PSR ovarian cancer support the primary analysis. Efficacy was observed in all cohorts, particularly in the gBRCAm and sBRCAm cohorts, where similar efficacy was observed. For patients without a <i>BRCA</i>m, greater efficacy was seen in the HRD-positive cohort.

Radiofrequency ablation for the treatment of recurrent gynecological malignancies

Objectives: To evaluate the safety and efficacy of radiofrequency ablation (RFA) and microwave ablation (MWA) for the treatment of isolated lesions in patients with recurrent gynecological malignancy. Methods: All patients with a gynecologic malignancy treated with RFA or MWA from 2007 to 2020 were evaluated. Ablations were performed using standardized technique under conscious sedation with CT or US image guidance by interventiomal radiology (IR). The primary endpoint was objective response rate (ORR). Secondary endpoints included response duration (DOR), clinical benefit rate (CBR), progression free survival (PFS), and safety. Deauville criteria was used to assess treatment response. Results: Thirty-two patients (17 ovarian, 7 endometrial, 8 cervical) were identified to have received ablative therapy for treatment of oligometastatic recurrences. Patients received a median of 2 (range 1-12) prior lines of chemotherapy. Of the 32 patients, 15 (47%) received concurrent systemic therapy at time of ablation (Table 1). Median PFS for the entire cohort was 7.3 (1.4-64.7) months. PFS was not significantly improved by concurrent systemic treatment (HR = 1.7, 95% CI: 0.79-3.83). Fourteen patients had complete response (CR), 2 had partial response (PR), and 6 had stable disease at time of initial follow-up imaging (median 3 months). CBR was 63% (n=20) at 16 weeks. No major complications occurred with only two patients reporting pain or weakness at the site of ablation. Conclusions: RFA and MWA is safe, well-tolerated, and demonstrated meaningful responses with 63% of patients experiencing clinical benefit at 16 weeks. Ablative therapy can be considered for the treatment of isolated lesions in patients with recurrent gynecologic malignancies. To evaluate the safety and efficacy of radiofrequency ablation (RFA) and microwave ablation (MWA) for the treatment of isolated lesions in patients with recurrent gynecological malignancy. All patients with a gynecologic malignancy treated with RFA or MWA from 2007 to 2020 were evaluated. Ablations were performed using standardized technique under conscious sedation with CT or US image guidance by interventiomal radiology (IR). The primary endpoint was objective response rate (ORR). Secondary endpoints included response duration (DOR), clinical benefit rate (CBR), progression free survival (PFS), and safety. Deauville criteria was used to assess treatment response. Thirty-two patients (17 ovarian, 7 endometrial, 8 cervical) were identified to have received ablative therapy for treatment of oligometastatic recurrences. Patients received a median of 2 (range 1-12) prior lines of chemotherapy. Of the 32 patients, 15 (47%) received concurrent systemic therapy at time of ablation (Table 1). Median PFS for the entire cohort was 7.3 (1.4-64.7) months. PFS was not significantly improved by concurrent systemic treatment (HR = 1.7, 95% CI: 0.79-3.83). Fourteen patients had complete response (CR), 2 had partial response (PR), and 6 had stable disease at time of initial follow-up imaging (median 3 months). CBR was 63% (n=20) at 16 weeks. No major complications occurred with only two patients reporting pain or weakness at the site of ablation. RFA and MWA is safe, well-tolerated, and demonstrated meaningful responses with 63% of patients experiencing clinical benefit at 16 weeks. Ablative therapy can be considered for the treatment of isolated lesions in patients with recurrent gynecologic malignancies.

Olaparib treatment in patients with platinum-sensitive relapsed ovarian cancer by BRCA mutation and homologous recombination deficiency status: secondary safety results from the phase II LIGHT study

Objectives: LIGHT (NCT02983799) evaluated olaparib treatment in patients with platinum-sensitive relapsed (PSR) ovarian cancer by BRCA mutation (BRCAm) and homologous recombination repair deficiency (HRD) status; the primary analysis demonstrated objective response rates (ORRs) of 69%, 64%, 29%, and 10% in cohorts of patients with a germline (g) BRCAm, with tumors with somatic (s) BRCAm, HRD-positive (non-BRCAm), and HRD-negative status, respectively (Cadoo K et al. ASCO 2020). Here, we report pre-specified secondary efficacy endpoints and subgroup analyses. Methods: In this open-label, non-randomized study, patients with PSR ovarian cancer and ≥1 prior line of platinum-based chemotherapy received olaparib monotherapy (300 mg bid). Patients were assigned to one of four cohorts based on whether they had a gBRCAm, tumors with sBRCAm, had HRD-positive (non-BRCAm) tumors, or HRD-negative tumors. Testing for gBRCAm was completed using Myriad BRACAnalysis CDx; sBRCAm testing was done with Myriad myChoice CDx. Genomic instability (GI) was assessed using the Myriad myChoice HRD test; tumors were deemed HRD-positive if they had a GI score ≥42. Secondary efficacy endpoints included investigator-assessed progression-free survival (PFS; RECIST v1.1) and cancer antigen (CA)-125 response. Time to any progression (TTAP) was calculated from the date of the first dose of olaparib until the earliest date of RECIST v1.1 or CA-125 disease progression, or death. Results: Conclusions: Secondary efficacy data and subgroup analyses from the LIGHT study of olaparib monotherapy as treatment for PSR ovarian cancer support the primary analysis. Efficacy was observed in all cohorts, particularly in the gBRCAm and sBRCAm cohorts, where similar efficacy was observed. For patients without a BRCAm, greater efficacy was seen in the HRD-positive cohort. LIGHT (NCT02983799) evaluated olaparib treatment in patients with platinum-sensitive relapsed (PSR) ovarian cancer by BRCA mutation (BRCAm) and homologous recombination repair deficiency (HRD) status; the primary analysis demonstrated objective response rates (ORRs) of 69%, 64%, 29%, and 10% in cohorts of patients with a germline (g) BRCAm, with tumors with somatic (s) BRCAm, HRD-positive (non-BRCAm), and HRD-negative status, respectively (Cadoo K et al. ASCO 2020). Here, we report pre-specified secondary efficacy endpoints and subgroup analyses. In this open-label, non-randomized study, patients with PSR ovarian cancer and ≥1 prior line of platinum-based chemotherapy received olaparib monotherapy (300 mg bid). Patients were assigned to one of four cohorts based on whether they had a gBRCAm, tumors with sBRCAm, had HRD-positive (non-BRCAm) tumors, or HRD-negative tumors. Testing for gBRCAm was completed using Myriad BRACAnalysis CDx; sBRCAm testing was done with Myriad myChoice CDx. Genomic instability (GI) was assessed using the Myriad myChoice HRD test; tumors were deemed HRD-positive if they had a GI score ≥42. Secondary efficacy endpoints included investigator-assessed progression-free survival (PFS; RECIST v1.1) and cancer antigen (CA)-125 response. Time to any progression (TTAP) was calculated from the date of the first dose of olaparib until the earliest date of RECIST v1.1 or CA-125 disease progression, or death. Secondary efficacy data and subgroup analyses from the LIGHT study of olaparib monotherapy as treatment for PSR ovarian cancer support the primary analysis. Efficacy was observed in all cohorts, particularly in the gBRCAm and sBRCAm cohorts, where similar efficacy was observed. For patients without a BRCAm, greater efficacy was seen in the HRD-positive cohort.

Apatinib combined with pegylated liposomal doxorubicin (PLD) versus PLD for platinum-resistant recurrent ovarian cancer (APPROVE): a multicenter, randomized, controlled, open-label, phase II trial

Objectives: Anti-angiogenic therapy combined with chemotherapy could improve survival in patients with platinum-resistant ovarian cancer (OC). APPROVE was conducted to evaluate the efficacy and safety of apatinib, an oral tyrosine kinase inhibitor that selectively inhibits VEGFR-2, in combination with pegylated liposomal doxorubicin (PLD) in patients with platinum-resistant or refractory recurrent OC. Methods: Eligible patients were histologically confirmed non-mucinous ovarian, primary peritoneal cancer, or fallopian-tube cancer who had experienced disease progression during, or within 6 months of discontinuing, any prior line of platinum-based chemotherapy. Patients with at least 1 lesion (measurable and/or nonmeasurable) that could be accurately assessed at baseline by computed tomography/magnetic resonance imaging. Patients were randomly assigned (1:1) to receive PLD alone (Arm PLD, 40mg/m2 IV every 4 weeks for up to 6 cycles) or with apatinib 250mg orally once daily (Arm A-PLD) until disease progression, unacceptable toxicity, or consent withdrawal. Patients were stratified according to prior platinum-sensitive relapsed (yes vs no) and platinum-free interval (less than 3 vs 3 to 6 months from last platinum therapy to subsequent progression). The primary endpoint was progression-free survival (PFS) by RECIST 1.1 in the intent-to-treat population (ITT population). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety. Results: Between Mar 22, 2018, and Nov 16, 2020, 152 patients were enrolled and randomly assigned to receive A-PLD (n=78) or PLD (n=74). Median follow-up was 8.1months (IQR 3.7-12.8). Median PFS was 5.8 months with A-PLD therapy versus 3.3 months with PLD alone (HR 0.41, 95% CI 0.26-0.64, P=0.0001). In patients with evaluable disease (Arm A-PLD, n=61; Arm PLD, n=63), the ORR was 37.7% (23/61) versus 9.5% (6/63) for A-PLD and PLD, respectively (P=0.0002). The DCR of A-PLD and PLD arms were 82.0% (50/61) and 58.7% (37/63), respectively (P=0.0050). Overall survival data are immature. Hypertension and hand-foot syndrome were more common with apatinib. No adverse events beyond expectation were reported. Conclusions: Apatinib in combination with PLD statistically significant prolonged PFS in patients with platinum-resistant or refractory recurrent ovarian cancer. ORR and DCR were also significantly improved. Adverse events were consistent with the established safety profiles of apatinib and PLD. Anti-angiogenic therapy combined with chemotherapy could improve survival in patients with platinum-resistant ovarian cancer (OC). APPROVE was conducted to evaluate the efficacy and safety of apatinib, an oral tyrosine kinase inhibitor that selectively inhibits VEGFR-2, in combination with pegylated liposomal doxorubicin (PLD) in patients with platinum-resistant or refractory recurrent OC. Eligible patients were histologically confirmed non-mucinous ovarian, primary peritoneal cancer, or fallopian-tube cancer who had experienced disease progression during, or within 6 months of discontinuing, any prior line of platinum-based chemotherapy. Patients with at least 1 lesion (measurable and/or nonmeasurable) that could be accurately assessed at baseline by computed tomography/magnetic resonance imaging. Patients were randomly assigned (1:1) to receive PLD alone (Arm PLD, 40mg/m2 IV every 4 weeks for up to 6 cycles) or with apatinib 250mg orally once daily (Arm A-PLD) until disease progression, unacceptable toxicity, or consent withdrawal. Patients were stratified according to prior platinum-sensitive relapsed (yes vs no) and platinum-free interval (less than 3 vs 3 to 6 months from last platinum therapy to subsequent progression). The primary endpoint was progression-free survival (PFS) by RECIST 1.1 in the intent-to-treat population (ITT population). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety. Between Mar 22, 2018, and Nov 16, 2020, 152 patients were enrolled and randomly assigned to receive A-PLD (n=78) or PLD (n=74). Median follow-up was 8.1months (IQR 3.7-12.8). Median PFS was 5.8 months with A-PLD therapy versus 3.3 months with PLD alone (HR 0.41, 95% CI 0.26-0.64, P=0.0001). In patients with evaluable disease (Arm A-PLD, n=61; Arm PLD, n=63), the ORR was 37.7% (23/61) versus 9.5% (6/63) for A-PLD and PLD, respectively (P=0.0002). The DCR of A-PLD and PLD arms were 82.0% (50/61) and 58.7% (37/63), respectively (P=0.0050). Overall survival data are immature. Hypertension and hand-foot syndrome were more common with apatinib. No adverse events beyond expectation were reported. Apatinib in combination with PLD statistically significant prolonged PFS in patients with platinum-resistant or refractory recurrent ovarian cancer. ORR and DCR were also significantly improved. Adverse events were consistent with the established safety profiles of apatinib and PLD.

H.O.P.E. & Healing: a randomized pilot study of structured palliative care referrals in recurrent ovarian cancer

<h3>Objectives:</h3> The inclusion of palliative care (PC) across the cancer continuum has been identified as a marker of high-quality cancer care. With limited PC specialists, integrated approaches may be necessary with the primary oncologist providing this care. However, recurrent ovarian cancer patients often have significant physical and/or emotional needs that may be best addressed by PC specialists. Our primary objective was to test the effect of a structured PC intervention on quality of life (QOL) for patients with recurrent ovarian cancer. Secondary objective was to assess the effect of the structured PC approach on overall survival. <h3>Methods:</h3> This was an IRB approved prospective randomized controlled trial at 2 academic institutions and was registered with clinicaltrials.gov (NCT02090582). Eligible patients included those with platinum resistant ovarian cancer or platinum sensitive cancer with a sentinel clinical event (recent bowel obstruction, liver metastases, pleural effusion or ascites). Subjects were randomized 1:1 to usual care versus a structured palliative care intervention (see Figure 1). Quality of life was assessed using the Functional Assessment of Cancer Therapy-Ovarian (FACT-O) and Functional Assessment of Chronic Illness Therapy-Palliative Care (FACIT-PAL) at baseline and 12-week intervals. Wilcoxon tests were used to detect differences between arms. Overall survival was analyzed using Kaplan-Meyer curves. <h3>Results:</h3> A total of 54 subjects were enrolled from 5/2014-4/2016; 26 in the intervention arm and 28 in the control arm. Median follow up was 6.5 months (Range: 2-12months). Median age of subjects was 63 with an ECOG performance status of 1. The majority of patients were Caucasian (44; 81.5%) and had platinum resistant disease (37; 68.5%). Most patients had received between 1-3 prior lines of chemotherapy (34/54; 63%); 5 patients (9.2%) had received ≥6 lines of therapy. There was no difference in overall or subset QOL in patients receiving usual care compared to those in the structured PC arm (p=0.14). There were no differences in hospital admissions (p=0.96), days from last chemo to hospice admission (p=1.0), days from hospice admission to death (p=0.41), place of death (p=0.68) or number of PC appointments (p=0.30) between the two arms. Patients enrolled in the 2nd half of the cohort were more likely to die at home rather than in the hospital or inpatient hospice (p=0.01) compared to subjects enrolled early in the study period. 81% of subjects randomized to the intervention arm completed at least 1 QDACT assessment (range 1-17). Similarly, there was no overall survival difference between the 2 arms (9.3m vs 10.1m; p=0.21). <h3>Conclusions:</h3> Structured integrated approaches between gynecologic oncology providers and PC specialists are feasible. The QDACT tool may be an effective, standardized measure to assess cancer symptom burden over time in this population. Further study is needed to identify interventions and collaborations that may have the greatest impact on QOL for recurrent ovarian cancer patients.

Radiation therapy for vaginal and perirectal lesions in recurrent ovarian cancer

<h3>Objectives:</h3> The role for radiation therapy (RT) to treat ovarian cancer (OC) patients with locally recurrent vaginal/perirectal lesions remains unclear, though we hypothesize that these patients may be salvaged locally and gain long-term survival benefit. We aimed to describe our institutional outcomes using vaginal brachytherapy±intensity modulated radiation therapy (IMRT) to treat this population and report our in-field control rate, RT-related toxicities, post-RT chemotherapy-free interval (CFI), RT-related toxicities, progression-free survival (PFS), and overall survival (OS). We also studied the prognostic impact of platinum status immediately prior to RT. <h3>Methods:</h3> This is a single institution retrospective case series of 17 recurrent OC patients treated with brachytherapy±IMRT for vaginal and/or perirectal recurrences between January 2006 and November 2019. Intent of RT (palliative or definitive) was determined collaboratively by the treating gynecologic and radiation oncologists. PFS and OS were defined from date of RT completion to either progression or death/last follow-up, respectively. <h3>Results:</h3> This was a heavily pre-treated cohort (median 3 prior lines of chemotherapy, range 1-9), with a median follow-up of 28.4 months (range 4.5-166.4) after RT completion (Figure 1). Most patients had high-grade serous histology (9 of 17) with the remainder of patients even distributed between low-grade serous, clear cell, mixed, and carcinosarcoma. Eleven patients were treated with definitive intent, including 4 with isolated vaginal/perirectal disease. Three patients received concurrent chemotherapy or immunotherapy and RT. Four (23.5%) patients had in-field failures at 2.3, 10.9, 23.2, and 25.7 months post-RT, all of whom had been treated with definitive intent. The 9 patients who were platinum-sensitive prior to RT had similar median PFS (8.1 vs. 10.4 months, log-rank p=0.91), but longer OS (53.9 vs 16.5 months, log-rank p=0.03) compared to their platinum-resistant counterparts. Excluding patients with low-grade histology or who were treated with palliative RT, the median CFI was 12.6 months (range 1.3-31.7). When including all patients, the two patients with the longest CFI post-RT included a <i>BRCA2</i> mutation carrier with an isolated vaginal recurrence and a patient with a <i>MLH1</i> somatic mutation treated with concurrent RT and pembrolizumab. RT was well tolerated with 2 (12%) experiencing grade 3/4 gastrointestinal/genitourinary toxicities. <h3>Conclusions:</h3> RT to treat locally recurrent vaginal and perirectal lesions in heavily pre-treated OC patients is safe and may effectively provide locoregional control.

Role of involved-site radiation in the management of recurrent ovarian malignancies: a single institutional experience

Objectives: Radiation therapy is commonly used to preserve local control in patients with oligometastatic disease. The objective of this study was to evaluate our institutional experience utilizing involved-site radiation (ISRT) in the management of recurrent ovarian cancer. Methods: Twenty-eight patients with recurrent ovarian cancer treated with ISRT between 2008-2019 were identified from our institutional database. A retrospective review of patient charts was performed. ISRT was delivered to sites of gross disease for all the patients who developed localized oligorecurrence following prior lines of chemotherapy to preserve local control. Results: The median age of diagnosis was 53 years range (23-70 years). Serous cystadenocarcinoma was the most common histological type (60.7%), followed by endometroid (14.3%) and clear cell subtypes (10.7%). Most patients had stage 3C (46.4%) at initial diagnosis. Many patients (79%) underwent initial optimal debulking, followed by platinum-based adjuvant chemotherapy. ISRT was considered mostly for patients who had recurrent disease confined to the pelvis (85.7%). The median time from the initial diagnosis to the initiation of ISRT was 49 months, and the median follow-up time after ISRT was 9.5 months (range 0-51 months). Most of the patients had a median of 2 recurrences (range 0-8) before receiving ISRT. The median radiation dose was 48 Gy (range 38-66 Gy). The median time to initiate additional chemotherapy after the ISRT was 2 months (range 0-23 months). The one-year rates of local control and distal progression following ISRT were 78% and 64.7%, respectively. The one-year overall survival rate after completion of ISRT was 72.5%. A majority of patients with recurrent disease following ISRT were treated with additional chemotherapy (10/19), and one patient with an out of field recurrence was managed with complete resection of distal metastases. The median time to initiate additional chemotherapy after the ISRT was 2 months (range 0-23 months). All patients tolerated ISRT well, and no ≥ grade 3 toxicities were observed. Conclusions: ISRT in recurrent ovarian cancer offers reasonable local control in well-selected patients with oligo-recurrences of ovarian cancer. Treatment was well-tolerated and may offer an alternative to interval-debulking surgery or chemotherapy in selected patients.