Discontinuation Of First-line Therapy Research Articles

Incidence and reasons for discontinuation of first-line therapy in patients with multiple myeloma: results from a historical cohort, Brazil 2009-2020.

Multiple myeloma (MM) is an incurable hematological cancer requiring multiple lines of anti-myeloma regimens to promote disease remission and increase patient survival. The study assessed the incidence and reasons for discontinuation of first-line therapy in outpatients who started MM therapy in Belo Horizonte, Brazil from 2009 to 2020. A historical cohort study in which patients were followed from treatment initiation until discontinuation of first-line therapy. Discontinuation of first-line therapy was characterized as (i) discontinuation followed by a second-line therapy, and (ii) discontinuation that prevented patients from receiving a subsequent line of treatment. Non-parametric competing risk analysis with a 95% confidence interval estimated the cumulative incidences of discontinuation followed by a second-line therapy. The probability of discontinuation was compared according to selected variables using the Gray's test at a significance level of 5%. Approximately half of the participants (n = 260) were female and younger than 65 years. Discontinuation of first-line therapy followed by a second-line therapy accounted for 50.4% of the patients and occurred up to 30th month. The main reason for discontinuation not qualifying patients for receiving second-line therapy was to achieve a response to treatment. The maximum times for discontinuation not followed by a second-line therapy ranged from 12 to 20 months due to deaths or response to treatment. The probability of receiving second-line therapy was higher among patients initiating therapy in 2009-2014 and those not undergoing transplantation. In conclusion, discontinuation of first-line therapy followed by second-line treatment occurred as likely as the discontinuation not followed by a subsequent line.

Isolated Extramedullary (EMD) Blastic Transformation of Chronic Myeloid Leukemia (CML-BP) in the TKI Era: Characteristics, Treatments and Outcomes

Isolated Extramedullary (EMD) Blastic Transformation of Chronic Myeloid Leukemia (CML-BP) in the TKI Era: Characteristics, Treatments and Outcomes

Enzalutamide plus androgen deprivation therapy (ADT) versus flutamide plus ADT in men with castration-resistant prostate cancer (CRPC): AFTERCAB.

81 Background: Enzalutamide has been approved for the treatment of CRPC in Japan since 2014. This study compared the efficacy and safety of enzalutamide + ADT and flutamide + ADT in the treatment of men with CRPC who progressed despite combined androgen blockade with bicalutamide + ADT. The sequential order of treatment was also investigated. Methods: The open-label, Phase 4 AFTERCAB study (NCT02918968) was conducted from November 2016–March 2020 in Japanese men aged ≥20 years with asymptomatic or mildly symptomatic CRPC (metastatic or nonmetastatic) and an Eastern Cooperative Oncology Group performance status of 0 or 1 who progressed despite bicalutamide + ADT. Patients were initially randomized to enzalutamide (160 mg/day) + ADT (enzalutamide first) or flutamide (375 mg/day [125 mg 3 × daily]) + ADT (flutamide first) as first-line therapy. Following prostate-specific antigen (PSA) progression, other disease progression, or discontinuation of first-line therapy due to an adverse event (AE), patients switched to the other treatment as second-line therapy. The primary endpoint was time to PSA progression with first-line therapy (TTPP1). Secondary endpoints included TTPP2 (TTPP1 + time to PSA progression with second-line therapy). AEs were monitored to assess safety. Results: 206 men were randomized, stratified by study site and disease stage. Baseline demographics and disease characteristics were similar between treatment arms. Median treatment exposure was 14.3 months (range 0.8–35.9) with enzalutamide first and 5.6 months (range 0.3–37.7) with flutamide first. 133 patients transitioned to second-line therapy (n=48 for enzalutamide first and n=85 for flutamide first). TTPP1 was significantly improved with enzalutamide first versus flutamide first; numerically longer TTPP2 was observed with enzalutamide first versus flutamide first (Table). With first-line therapy, 92.2% (n=94) of patients reported treatment-emergent AEs (TEAEs) and 28.4% (n=29) reported serious TEAEs for enzalutamide first. Corresponding numbers for flutamide first were 76.0% (n=79) for TEAEs and 14.4% (n=15) for serious TEAEs. Conclusions: Treatment with enzalutamide + ADT provided a significant improvement in time to PSA progression versus flutamide + ADT as first-line therapy. Both treatments were generally well tolerated, with AEs consistent with the known safety profiles. Clinical trial information: NCT02918968. [Table: see text]

Clinical and Pathological Characteristics of Metastatic Renal Cell Carcinoma Patients Needing a Second-Line Therapy: A Systematic Review.

Simple SummaryThe management of metastatic renal cell carcinoma (mRCC) represents a clinical challenge. Progression or toxicity may occur during first-line treatments and many patients require a second-line option. Given the expanding options for second-line therapies clinicians are faced with the challenge to individualize treatment. We performed a systematic review in order to summarize available evidences about the clinicopathological profile of mRCC patients who receive a second-line therapy. We identified twenty-nine studies enrolling 7650 patients. Discontinuation of first-line therapy was due to progression in the majority of patients with 77.8% patients harboring ≥2 metastatic sites. Most patients had a good performance status, their age ranged from 55 to 70 years and their prognostic profile revealed a good or intermediate disease in most cases. Tailoring of second-line treatment strategies based on these features is strongly advocated.A high percentage of patients with metastatic renal cell carcinoma (mRCC) require a second-line option. We aimed to summarize available evidences about the clinicopathological profile of mRCC patients who receive a second-line therapy. A systematic review was performed in August 2020. We included papers that met the following criteria: original research; English language; human studies; enrolling mRCC patients entering a second-line therapy. Twenty-nine studies enrolling 7650 patients (73.5% male, mean age: 55 to 70 years) were included. Clear cell histology was reported in 74.4% to 100% of cases. Tyrosine kinase inhibitors, immunotherapy, bevacizumab, mTOR inhibitors, and chemotherapy were adopted as first line option in 68.5%, 29.2%, 2.9%, 0.6%, and 0.2% of patients, respectively. Discontinuation of first-line therapy was due to progression and toxicity in 18.4% to 100% and in 17% to 48.8% of patients, respectively. Eastern Cooperative Oncology Group performance status score was 0 or 1 in most cases. Most prevalent prognostic categories according to the International Metastatic RCC Database Consortium and Memorial Sloan–Kettering Cancer Centre score were intermediate and good. About 77.8% of patients harboured ≥2 metastatic sites. In conclusion, patients who enter a second-line therapy are heterogeneous in terms of a clinical-pathological profile. Tailoring of second-line treatment strategies is strongly advocated.

Real-World Outcomes and Factors Associated With the Second-Line Treatment of Patients With Gastric, Gastroesophageal Junction, or Esophageal Adenocarcinoma.

This retrospective observational study was designed to evaluate overall survival in a real-world patient population and to identify predictive factors associated with receipt of second-line therapy. A retrospective analysis of electronic medical records (Flatiron Health, New York) was conducted among patients initiating first-line therapy from January 1, 2013, through April 30, 2018. Eligible patients were diagnosed with advanced gastric, gastroesophageal junction, or esophageal adenocarcinoma and ≥18 years of age at the time of treatment initiation. Patients alive 45 days after discontinuation of first-line therapy were considered potentially eligible for continued therapy and were categorized into those who received and those who did not receive second-line therapy. Survival analyses were conducted using Kaplan-Meier method and log-rank test without adjusting for any baseline covariates. Factors associated with further treatment were evaluated using logistic regression. A total of 3850 patients met eligibility criteria. Among the 2516 patients available to receive second-line therapy, 1515 (60.2%) received second-line therapy and 1001 (39.8%) did not receive further therapy. Among those potentially eligible to receive second-line therapy, median survival was 15.4 months (95% confidence interval [CI]: 14.6-16.0) from initiation of first-line therapy for those who received second-line therapy and 10.0 months (95% CI: 9.3-10.7) for those who did not. Longer duration of first-line therapy (≥169 vs ≤84 days), HER2-positive tumors, initially diagnosed with stage IV disease, less weight loss during first-line therapy, and younger age were associated with receipt of second-line therapy (all P < .001). Longer survival was associated with multiple lines of therapy; however, these results should be interpreted with caution, and no causal relationship can be inferred.

P2.03a-043 A Retrospective Analysis of the Chemotherapy for ‘Very Old' Patients Aged 80 Years and Order with Advanced Lung Cancer: Topic: Clinical Trials

The number of elderly patients with lung cancer is increasing, and it is becoming a public health problem in Japan. There is little data on the efficacy and safety of chemotherapy for patients aged 80 and older, even though they constitute 30% of all lung cancer incidence (80-84 years, 16%; 85years and older, 14.4%) reported by cancer information service, National Cancer Center, Japan in 2012. The objective of this study was to evaluate the efficacy and safety of chemotherapy in patients aged 80 and older with advanced lung cancer in our hospital, retrospectively. The medical records were analyzed from January 2010 to July 2016. In total, 27 patients were analyzed. Patient characteristics were below; the median ages were 81 years (range, 80-84); female/ male: 8/19, PS 0-1/ 2: 22/5, adenocarcinoma/ squamous/ NOS (not otherwise specified) /SCLC: 7/8/1/11, stageIII/ IV/ recurrence: 3/19/5. Platinum-doublets, mono-chemotherapy were used in 15, 12 patients, respectively. In platinum-doublets, the median number of cycle was 4 (range 1-6) and dose reduction was conducted in 4 of 11 patients (36%) receiving at least 2 cycles. CBDCA+ETP was administered for 11 SCLC patients. The response rate was 45% and median PFS was 4.1months (95% CI: 1.2-4.9). Four patients with NSCLC used platinum-doublets; CBDCA+nab-PTX/ CBDCA+PEM: 1/3. There were no patients who achieved objective response and the median PFS was 3.0 months (95% CI: 2.2-6.5). Among 2 of 4 patients, treatment discontinuation due to the deterioration of depression and bone fracture arose. Treatment related death (TRD) was observed in 2 patients with PS-2 (13%). Mono-chemotherapy was administered in 12 patients; VNR/ DTX/ PEM: 7/ 4/ 1. The median number of cycle was 3.5 (range 1-13) and dose reduction was conducted in 2 patients (20%). No TRD was observed. The response rate and disease control rate was 8% and 91%, and median PFS was 6.4months (95% CI: 1.8-12.2). Grade 3 or more hematological toxicities tended to be more frequent in platinum-doublets than mono-chemotherapy, but febrile neutropenia was frequent in both groups; neutropenia 93%/75%, thrombocytopenia 33%/0%, febrile neutropenia 20%/33%. After discontinuation of first line therapy, the subsequent chemotherapy was more frequently administered in mono-chemotherapy than platinum-doublets (58% vs 40%). The chemotherapy for patients aged 80 and older could be well tolerated in most cases, but patient selection should be more carefully conducted than younger patients.

Efficacy, tolerability, and biomarker analyses from a phase III, randomized, placebo-controlled, parallel group study of gefitinib as maintenance therapy in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC; INFORM; C-TONG 0804).

LBA7511 Background: INFORM (a phase III, randomized, multicenter, parallel group study; NCT00770588 ) investigated the efficacy, safety and tolerability of gefitinib (G) vs. placebo (P) as maintenance therapy in pts with locally advanced/metastatic NSCLC following standard first-line platinum based chemotherapy. Methods: Pts (≥18 years, with stage IIIB/IV NSCLC and WHO performance status 0-2) had completed 4 cycles of first-line platinum based doublet chemotherapy without progression/unacceptable toxicity. Pts were randomized 1:1 to G 250mg/day or P on discontinuation of first-line therapy. Progression-free survival (PFS; primary endpoint) was assessed in the intent to treat population (Cox proportional hazards adjusted for histology [adenocarcinoma vs. non-adenocarcinoma], smoking status [never-smoker vs. smoker], EGFR mutation status [positive vs. negative vs. unknown] and best response to first-line chemotherapy [complete response/partial response vs. stable disease]). PFS was considered superior with gefitinib if the G:P hazard ratio (HR) upper confidence interval (CI) was &lt;1.00. Secondary endpoints included overall survival (OS), objective response rate, disease control rate, symptom improvement and tolerability. Results: 296 pts (n=148 G, n=148 P) were randomized (27 centers in china; 26 September 2008-10 August 2009). PFS data cutoff on 24 January 2011. Median duration of follow-up was 16.8 months: 91% pts progressed; 59% deaths. Demography was balanced between treatments; overall, 54.1% pts were never-smokers, 70.6% had adenocarcinoma, and 40.9% were female. For G vs. P, PFS HR=0.42; 95% CI 0.32-0.54; p&lt;0.0001; median PFS 4.8 vs. 2.6 months. Most common AEs (any grade) with G were rash (49.7%), diarrhea (25.2%), and ALT increase (21.1%) which were generally mild/moderate. Overall incidence of serious AEs: G (6.8%); P (3.4%). Other secondary endpoint data (including OS and biomarkers) will be presented. Conclusions: PFS was significantly longer with G compared with P as maintenance therapy in Chinese patients with locally advanced NSCLC.

Small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up