Updated report of a phase II randomized trial of transoral surgical resection followed by low-dose or standard postoperative therapy in resectable p16+ locally advanced oropharynx cancer: A trial of the ECOG-ACRIN cancer research group (E3311).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6010-6010
Author(s):  
Robert L. Ferris ◽  
Yael Flamand ◽  
Gregory S. Weinstein ◽  
Shuli Li ◽  
Harry Quon ◽  
...  
Keyword(s):  
Phase Ii ◽  
Standard Dose ◽  
Locally Advanced ◽  
Oncologic Outcome ◽  
Smoking History ◽  
Transoral Surgery ◽  
P Value ◽  
Oropharynx Cancer ◽  
Patient Reported

6010 Background: Definitive or postoperative chemoradiation (CRT) is highly curative for human papillomavirus-associated (HPV+) oropharynx cancer (OPC) but induces significant toxicity. As a potential deintensification strategy, we studied primary transoral surgery (TOS) and, in intermediate pathologic risk patients, reduced dose postoperative RT (PORT). Methods: E3311 is a phase II trial with randomization to reduced- or standard-dose PORT for resected stage III-IVa (AJCC7) intermediate pathologic risk HPV+ OPC, stratified by smoking history. Primary endpoints have been reported; we now present updated 3-year PFS and patient-reported outcomes (PRO), including head and neck-cancer specific quality of life (FACT-H&N) and swallowing perception and performance (MDADI). Results: Of 519 enrolled patients, 495 underwent TOS. The primary oncologic endpoint was 2-year PFS for 50 Gy (Arm B) or 60Gy (Arm C). Among 360 eligible and treated patients (ETP), Arm A (observation, N = 38) enrolled 11%, Arms B (N = 100) or C (N = 109) randomized 58%, and Arm D (66Gy + weekly cisplatin, N = 113) enrolled 31%. With 35.1 months median follow-up, 3-year PFS Kaplan-Meier estimate is 96.9% (90% CI [91.9%, 100%]) for Arm A; 94.9% (90% CI [91.3%, 98.6%]) for Arm B; 93.5% (90% CI [89.4%, 97.9%]) for Arm C; and 90.7% (90% CI [86.2%, 95.4%]) for Arm D. Recurrences and death without recurrence were 4 and 1 in Arm B, and 5 and one in Arm C. Smokers ( > 10 pack-years) did not have worse 3-year PFS in Arms B or C. Treatment arm distribution and outcome for ineligible patients who started adjuvant therapy mirrored the 360 ETP. A comparison combining arms B/C versus arm D in the proportion of patients stable/improved in FACT-H&N total score, from baseline to 6 months post-treatment as a pre-specified endpoint, was 56% vs. 38% (p value = 0.011, one-sided Fisher’s exact test); however, underlying differences in treatment and risk may be confounding. An exploratory comparison between Arms B and C revealed improvement in FACT H&N (63% in Arm B vs. 49% in Arm C had a stable/improved score, p-value = 0.056). Conclusions: Primary TOS and reduced PORT retained outstanding oncologic outcome at 35 months follow up, with favorable QOL and functional outcomes, in intermediate risk HPV+ OPC. Clinical trial information: NCT 01898494.

Transoral robotic surgical resection followed by randomization to low- or standard-dose IMRT in resectable p16+ locally advanced oropharynx cancer: A trial of the ECOG-ACRIN Cancer Research Group (E3311).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6500-6500 ◽  
Author(s):  
Robert L. Ferris ◽  
Yael Flamand ◽  
Gregory S. Weinstein ◽  
Shuli Li ◽  
Harry Quon ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Standard Dose ◽  
Locally Advanced ◽  
Operative Therapy ◽  
Phase Iii ◽  
Smoking History ◽  
Transoral Surgery ◽  
Intermediate Risk ◽  
Oropharynx Cancer ◽  
Transoral Resection

6500 Background: ECOG-ACRIN 3311 examines reduced postoperative therapy in patients with “intermediate risk” p16+ oropharynx cancer (OPC) undergoing primary transoral surgical management. We report the primary endpoint of 2-year progression free survival (PFS) for patients randomized to 50Gy vs 60Gy without chemotherapy. Methods: Between December 2013 and July 2017, 82 credentialed surgeons performed transoral resection (TOS) for 519 OPC patients (cT1-2 stage III/IV AJCC7 without matted neck nodes); post-operative management was determined by pathologically assessed risk. Among 353 eligible and treated patients, Arm A enrolled 10% (N=37) for clear margins, 0-1 nodes, no extranodal extension (ENE)), Arms B (50Gy, N=102) or C (60Gy, N=104) randomized 58%, for clear/close margins, 2-4 + nodes, or ENE ≤1mm, while Arm D (N=110, 60-66Gy plus weekly cisplatin, 40 mg/m2, positive margin with any T stage, >4 + nodes, or >1mm ENE) enrolled 31%. Arm D assignment was based on >1mm ENE (76%), > 4 nodes (27%), and/or positive margins (11%). Intermediate-risk patients were stratified by smoking history (>10 pk-yr). Of the 80 pts (15%) deemed ineligible, 28 had scans/labs not done per protocol, however treatment arm distribution for all patients mirrored that for the 353 pts eligible and treated. Results: Median follow-up was 31.8 months. 2 yr PFS for Arms A, B and C were 93.9% (90% CI=87.3%, 100%), 95.0% (90% CI=91.4%, 98.6%) and 95.9% (90% CI=92.6%, 99.3%) respectively, while Arm D was 90.5% (90% CI=85.9%, 95.3%). The regimen of TOS + low-dose radiation is considered worthy of further study, since the primary endpoint of the upper bound of the 90% CI (in the intermediate risk group) exceeding 85% was met. Of 17 progression events, 7 were locoregional. There were 10 distant recurrences: Arm A=1, Arm B=2, Arm C=4, Arm D=3. Grade III/IV treatment-related AE rates were 15%/2% during surgery, 13%/2% for Arm B and 25%/0% for Arm C. There were 2 treatment-related deaths (one surgical and one Arm D). Conclusions: Transoral resection of p16+ OPC is safe and results in good oncologic outcome, presenting a promising deintensification approach. For patients with low-risk disease, 2-yr PFS is favorable without post-operative therapy. For those with uninvolved surgical margins, <5 involved nodes, and minimal (<1mm) ENE, reduced dose postoperative RT without chemotherapy appears sufficient. Transoral surgery plus 50Gy should be compared to optimal non-surgical therapy in a phase III trial. Clinical trial information: NCT01898494 .

scholarly journals Intermediate to Long Term Follow Up of Hintegra Total Ankle Replacements

2019 ◽  
Vol 4 (4) ◽  
pp. 2473011419S0043
Author(s):  
Andrew Walls ◽  
Gavin Heyes ◽  
Raymond McKenna ◽  
Honor Prout ◽  
R Alistair Wilson ◽  
...  
Keyword(s):  
Learning Curve ◽  
Smoking History ◽  
P Value ◽  
Ankle Arthritis ◽  
Aofas Score ◽  
Additional Surgery ◽  
Patient Reported ◽  
One Way Anova

Category: Ankle, Ankle Arthritis Introduction/Purpose: The optimal management of severe ankle arthritis is still debated. Some maintain that arthrodesis is the reference standard. However, with appropriately selected patients modern Total Ankle Replacements (TAR) can offer good to excellent patient reported outcomes. First generation TARs were highly constrained and prone to accelerated wear, loosening and subsidence and failure. Subsequent reincarnations have led to the development of reduced constraint, mobile bearing prostheses with reliance on ligamentous balancing. New generation TARs report 10-year survival of up to 89%, however many studies are from design centres and not uniformly replicated elsewhere. The largest long-term Hintegra TAR study is from a designer’s centre, reporting 84% survival at 10 years. This paper reports multicentre results on the intermediate (6 years +) outcomes of the Hintegra TAR. Methods: TARs performed by two senior consultant surgeons from 30/03/2004-18/01/2013 were reviewed. Prospective review of patients included; review of current and or new symptoms, an updated past medical history, AOFAS Hindfoot scores and radiological imaging. We used the AOFAS hindfoot score for our functional assessment as it validated and also the most frequently cited scoring system in the literature. Radiographs were reviewed for loosening and this was defined by a validated assessment method with a suitably low inter-observer variability. In our study all images were reviewed by at least two authors for a consensus opinion. The Charlson Comorbidity Index (CCI) was utilised to evaluate and risk stratify co-morbidities and their influence on other illnesses and surgical outcomes. This study was considered to be service evaluation by our local research and ethics department and approved in accordance with General Data Protection Regulation guidelines. Statistical analysis was performed using SPSS software. Results: 62 TARs were performed on 58 patients. Excluding the deceased (n=9) and patients lost to follow up (n=1), mean follow up was 12years 3months. AOFAS score did not decline with age of TAR (Spearman Rho co-efficient 0.339). During the first 4 years Hintegra TARs were performed 11/23 (48%) patients underwent additional surgery highlighting the already published learning curve with TAR. 5-year and 10-year survival was 84% (52/62) and 71% respectively (27/38). Predictors for revision included obesity with a BMI>30 versus those with a BMI of 18.5-25 (Chi-Sq P-value 0.006) and previous smoking history (Chi-Sq P-value 0.027). No association was found between CCI scores and revision (One-way ANOVA P-value 0.4). Interestingly lower ASA scores were significantly more likely to require revision (One-way ANOVA P-value 0.034). Conclusion: The Hintegra Total Ankle Replacement offers good sustained pain relief and function. 71% of implants were retained with an average AOFAS score of 78 (36-100 range) after 10 years. We do recommend caution in patients who are obese, smokers, ex-smokers and those with a high functional demand. We stress the importance of achieving correct alignment of the TAR to maximise longevity. There is a steep learning curve when performing a TAR and we would suggest operating with another experienced surgeon for at least the first 20 cases.

scholarly journals Clinical Radiographical Outcomes and Complications after a Brand-New Total Ankle Replacement Design through an Anterior Approach: A Retrospective at a Short-Term Follow Up

2021 ◽  
Vol 10 (11) ◽  
pp. 2258
Author(s):  
Massimiliano Mosca ◽  
Silvio Caravelli ◽  
Emanuele Vocale ◽  
Simone Massimi ◽  
Davide Censoni ◽  
...  
Keyword(s):  
Mean Value ◽  
Total Ankle Replacement ◽  
P Value ◽  
Ankle Osteoarthritis ◽  
Ankle Replacement ◽  
Patient Reported ◽  
End Stage ◽  
Term Performance ◽  
Replacement Design

Recently, the progress in techniques and in projecting new prosthetic designs has allowed increasing indications for total ankle replacement (TAR) as treatment for ankle osteoarthritis. This retrospective work comprehended 39 subjects aged between 47 and 79 years old. The patients, observed for at least 12 months (mean follow up of 18.2 ± 4.1 months), have been evaluated according to clinical and radiological parameters, both pre- and post-operatively. The AOFAS and VAS score significantly improved, respectively, from 46.2 ± 4.8 to 93.9 ± 4.1 and from 7.1 ± 1.1 to 0.7 ± 0.5 (p value < 0.05). At the final evaluation, the mean plantarflexion passed from 12.2° ± 2.3° to 18.1° ± 2.4° (p value < 0.05) and dorsiflexion from a pre-operative mean value of 8.7° ± 4.1° to 21.7° ± 5.4° post-operatively (p value < 0.05). This study found that this new total ankle replacement design is a safe and effective procedure for patients effected by end-stage ankle osteoarthritis. Improvements have been demonstrated in terms of range of motion, radiographic parameters and patient-reported outcomes. However, further studies are needed to assess the long-term performance of these prostheses.

Phase II Randomized Trial of Transoral Surgery and Low-Dose Intensity Modulated Radiation Therapy in Resectable p16+ Locally Advanced Oropharynx Cancer: An ECOG-ACRIN Cancer Research Group Trial (E3311)

2021 ◽  
Author(s):  
Robert L. Ferris ◽  
Yael Flamand ◽  
Gregory S. Weinstein ◽  
Shuli Li ◽  
Harry Quon ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Cancer Therapy ◽  
Randomized Trial ◽  
Functional Assessment ◽  
Oncologic Outcome ◽  
Progression Free Survival ◽  
Transoral Surgery ◽  
Intermediate Risk ◽  
Free Survival ◽  
Oropharynx Cancer

PURPOSE Definitive or postoperative chemoradiation (CRT) is curative for human papillomavirus–associated (HPV+) oropharynx cancer (OPC) but induces significant toxicity. As a deintensification strategy, we studied primary transoral surgery (TOS) and reduced postoperative radiation therapy (RT) in intermediate-risk HPV+ OPC. METHODS E3311 is a phase II randomized trial of reduced- or standard-dose postoperative RT for resected stage III-IVa (American Joint Committee on Cancer-seventh edition) HPV+ OPC, determined by pathologic parameters. Primary goals were feasibility of prospective multi-institutional study of TOS for HPV+ OPC, and oncologic efficacy (2-year progression-free survival) of TOS and adjuvant therapy in intermediate-risk patients after resection. TOS plus 50 Gy was considered promising if the lower limit of the exact 90% binomial confidence intervals exceeded 85%. Quality of life and swallowing were measured by functional assessment of cancer therapy-head and neck and MD Anderson Dysphagia Index. RESULTS Credentialed surgeons performed TOS for 495 patients. Eligible and treated patients were assigned as follows: arm A (low risk, n = 38) enrolled 11%, intermediate risk arms B (50 Gy, n = 100) or C (60 Gy, n = 108) randomly allocated 58%, and arm D (high risk, n = 113) enrolled 31%. With a median 35.2-month follow-up for 359 evaluable (eligible and treated) patients, 2-year progression-free survival Kaplan-Meier estimate is 96.9% (90% CI, 91.9 to 100) for arm A (observation), 94.9% (90% CI, 91.3 to 98.6]) for arm B (50 Gy), 96.0% (90% CI, 92.8 to 99.3) for arm C (60 Gy), and 90.7% (90% CI, 86.2 to 95.4) for arm D (66 Gy plus weekly cisplatin). Treatment arm distribution and oncologic outcome for ineligible or step 2 untreated patients (n = 136) mirrored the 359 evaluable patients. Exploratory comparison of functional assessment of cancer therapy-head and neck total scores between arms B and C is presented. CONCLUSION Primary TOS and reduced postoperative RT result in outstanding oncologic outcome and favorable functional outcomes in intermediate-risk HPV+ OPC.

Health-related quality-of-life (HRQoL) analysis from a randomized phase II trial of androgen signaling inhibitors with or without androgen deprivation therapy (ADT) for castration-sensitive prostate cancer: LACOG 0415.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 64-64
Author(s):  
Andrey Soares ◽  
Diogo Assed Bastos ◽  
Fabio A. B. Schutz ◽  
Eduardo Cronemberger ◽  
Murilo Luz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Locally Advanced ◽  
Patient Reported Outcome ◽  
Abiraterone Acetate ◽  
Outcome Data ◽  
Rank Test ◽  
Emotional Wellbeing ◽  
Patient Reported ◽  
Related Quality

64 Background: LACOG0415 is a 3-arm randomized trial evaluating ADT with abiraterone acetate plus prednisone (ADT+AAP), apalutamide alone (APA) or apalutamide with AAP (APA+AAP) for patients with locally-advanced, high-risk biochemical recurrence or metastatic castration-sensitive prostate cancer (ASCO 2020). In this trial, ADT+AAP and APA+AAP achieved the primary endpoint of percentage of patients with PSA ≤ 0.2 ng/mL at week 25. Apalutamide alone showed a high PSA decline > 50% rate, but did not achieve the pre-specified PSA threshold. Here we report patient-reported outcome data using Functional Assessment of Cancer Therapy-Prostate (FACT-P). Methods: HRQoL was measured in the overall population using the FACT-P questionnaire, comprising 5 subscales: physical wellbeing (PWB), functional wellbeing (FWB), emotional wellbeing (EWB), social/family wellbeing (SFWB), and prostate cancer subscale (PCS). Scores for each patient were measured at baseline and every four weeks until week 25. Questionnaire completion was defined as ≥ 1 question answered at an assessment time point. Analysis of HRQoL change from baseline and deterioration included only patients with baseline and ≥ 1 postbaseline score. Differences greater than 10-points in FACT-P total score and differences greater than 3-points in PWB, FWB, EWB, SFWB, and PCS scores were considered clinically significant. The time-to-event endpoint was estimated by Kaplan-Meier method and compared by stratified log-rank test. Results: 128 patients were included in LACOG0415 trial and 122 of them completed the HRQoL assessments (ranging from 95.3% at baseline to 79.7% at week 25). FACT-P and all subscales scores were similar for all three arms at baseline. There were no meaningful differences in FACT-P scores at baseline and at week 25 between the 3 arms. The subscales scores also showed no statistically differences at baseline and at week 25. Time to FACT-P deterioration did not show any statistically difference between three arms ( P=0.3371). Conclusions: ADT free alternatives with APA alone or APA+AAP did not show meaningful differences in HRQoL in patients with advanced castration-sensitive prostate cancer compared to ADT+AAP. The short follow-up period limited the ability to explore differences in HRQoL after 25 weeks. Larger studies with longer follow-up are needed to further evaluate HRQoL with ADT-free strategies. Clinical trial information: NCT02867020. [Table: see text]

scholarly journals Durability of Smoking Cessation for Elective Lower Extremity Orthopaedic Surgery

2019 ◽  
Vol 4 (4) ◽  
pp. 2473011419S0039
Author(s):  
Danica H. Smith ◽  
Michael F. McTague ◽  
Michael J. Weaver ◽  
Jeremy T. Smith
Keyword(s):  
Smoking Cessation ◽  
Lower Extremity ◽  
Orthopaedic Surgery ◽  
Perioperative Complications ◽  
Smoking History ◽  
Secondary Outcome ◽  
Impaired Wound Healing ◽  
Patient Reported ◽  
The Impact

Category: General Health Introduction/Purpose: Smoking tobacco is a risk factor for impaired wound healing, infection, delayed fracture healing, and prolonged hospital stay. Smoking cessation prior to surgery has shown a 40% relative risk reduction in total perioperative complications. The primary purpose of this study is to evaluate the impact of preoperative smoking cessation on long-term smoking habits in patients undergoing elective lower extremity orthopaedic surgery. The secondary outcome is patient-reported effectiveness of smoking cessation method. Methods: A retrospective cohort study was performed by identifying all patients who were smokers that were required to quit and subsequently had a normal nicotine/cotinine serum test prior to lower extremity orthopaedic surgery. Attempts were made to contact all patients and administer a survey inquiring about demographics, medical history, smoking history, smoking cessation process, and current smoking status. Results: Of 36 eligible patients, 23 completed the survey. Eleven patients identified as current non-smokers (48%) at the time of survey follow-up (mean follow-up 55 months with a range of 12 to 88 months). Of these 11, 82% said they were very likely to continue to refrain from smoking. Twelve patients identified as current smokers at the time of survey, over half of whom ceased smoking for at least three months perioperatively. The reasons for resuming smoking were “stress” (45%), ”falling back into the habit” (37%), and due to “friends who smoke” (18%). The majority of smoking patients (92%) decreased the number of cigarettes they smoked regularly. The most effective smoking cessation techniques were ”cold turkey”, “non-nicotine medication”, and ”trans-dermal nicotine patches”. Conclusion: Elective surgery offers a unique opportunity for smoking cessation. Of 23 patients required to quit smoking prior to surgery, 48% maintained smoking cessation at least one year postoperatively. Of the 12 patients who relapsed, 55% stated that they did not resume smoking until at least three months postoperatively, suggesting that this particular period may be an important time for intensified smoking cessation counseling.

Treatment of advanced non-small cell lung cancer (NSCLC) with a biweekly schedule of irinotecan (I), paclitaxel, and cisplatinum (P): A phase II study

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19076-e19076
Author(s):  
M. Gonzalez ◽  
J. Rebollo ◽  
R. Rami ◽  
J. Belda ◽  
J. Farré ◽  
...  
Keyword(s):  
Phase Ii ◽  
Advanced Nsclc ◽  
Phase Ii Study ◽  
Locally Advanced ◽  
Metastatic Tumor ◽  
Complete Response ◽  
Time To Progression ◽  
Good Tolerance ◽  
Confirmatory Phase

e19076 Background: Irinotecan, paclitaxel (taxol, T), and cisplatinum are among the most active agents in the treatment of NSCLC, given alone as single agents or in combination. Based in previous data (Proc ASCO 2003 # 2816), we performed a confirmatory phase II study of the activity of a bi-weekly combination of I (120 mg/m2), T(60 mg/m2) and P (40 mg/m2) in advanced NSCLC. Methods: Forty-three patients (pts) (37 male, 6 female) with histologically proven IIIA-IV NSCLC were treated at our institution. Median age was 61 years (33–79). All pts were ECOG 0–2. 14 pts had locally advanced disease (8 IIIA, 6 IIIB) and 29 metastatic disease. Previous treatments included surgery (5 pts), radiotherapy (4 pts), chemotherapy (5 pts), surgery + radiotherapy (3 pts) and surgery + chemotherapy (2 pt). In three cases, treatment was administered as adjuvant after resection of a primary (2 cases) or a metastatic tumor (1 case). Results: A total of 299 courses were administered (median 6, range 2–14). Toxic episodes grade III-IV were neutropenic fever (10/299; 3.3%), anemia (1/299; 0.3%), asthenia (3/299; 1%), diarrhea (5/299; 17%), hemorrhagic colitis (1/299; 0.3%), mucositis (2/299, 0.6%), vomiting (4/299; 1.3%) and peripheral neuropathy (1/299; 0.3%). With a median follow-up of 72 months (9–97), 2 pts (4.6%) presented pathological complete response, 26 (60%) partial response, 11 (25%) stable disease and 1 pt progressed. Four partial responders were rendered free of disease after rescue surgery. Median time to progression was 6 months. Median survival was 10 months. The actuarial 2 and 5-year overall survival are 26% and 13% respectively. Conclusions: I, T and P at the referred doses can be safely administered in a bi-weekly basis, with a good tolerance and response rate in advanced NSCLC pts. No significant financial relationships to disclose.

Cardiovascular events and clinical responses in prostate cancer patients treated with transcutaneous estrogen patches compared with LHRH analogues: Results from a randomized phase II trial (MRC PR09 PATCH).

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 201-201
Author(s):  
P. D. Abel ◽  
S. K. Sundaram ◽  
H. G. Kynaston ◽  
N. Clarke ◽  
A. A. Alhasso ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase Ii ◽  
Primary Outcome ◽  
Locally Advanced ◽  
Metabolic Effects ◽  
Smoking History ◽  
Attractive Potential ◽  
Secondary Outcome ◽  
Coronary Syndrome ◽  
Venous Thromboembolic Events

201 Background: Androgen-deprivation therapy (ADT) with a luteinising hormone-releasing hormone analogue (LHRHa) is widely used in the management of prostate cancer. LHRHa suppresses testosterone to castrate levels but can lead to long term toxicities including osteoporosis, adverse metabolic effects and cardiovascular (CV) complications. Transcutaneous oestrogen is an attractive potential alternative to ADT. This approach circumvents first-pass hepatic metabolism and so should avoid the CV effects previously reported with oral oestrogen in men with prostate cancer. Castrate levels of testosterone, and hence prostate cancer outcomes, are expected to be equivalent but the side-effects associated with ADT will potentially be avoided. Methods: PATCH is a multi-centre phase II randomized study of 254 men with locally advanced or metastatic prostate cancer assigned (2:1) to either oestrogen patches (Merck FemSeven 100mcg/24hr; 4 patches changed twice-weekly, reducing to 3 after 4 weeks) or LHRHa. The primary outcome is CV morbidity and mortality, including arterial and venous thromboembolic events, acute coronary syndrome and heart failure. These have been assessed by an independent committee, blind to the treatment arm. Secondary outcome measures include PSA response, serum testosterone and also toxicities. Results: Baseline data on the 254 men will be presented including age, cardiovascular risk factors (smoking history, lipid levels and family history), and stage/grade of tumour at presentation and randomisation. CV events will be presented by randomisation arm and by treatment at the time of the event. Data relating to rates of castrate levels of hormones, PSA responses, sexual dysfunction, other toxicities (including gynaecomastia, hot flushes, anaemia and bone fractures) and compliance will also be available. Conclusions: Providing the data demonstrate that the patches are a safe and potentially efficacious therapy we propose to recruit a further 410 patients with progression-free survival as the primary outcome. CV events will continue to be closely monitored, alongside other outcomes. [Table: see text]

Randomized phase II study of pharmacodynamic separation (PDS) of pemetrexed (Pem) and erlotinib (Erl) versus pem alone in patients (pts) with advanced non-small cell lung cancer (NSCLC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8097-8097 ◽  
Author(s):  
Tianhong Li ◽  
Bilal Piperdi ◽  
William Vincent Walsh ◽  
Mimi Kim ◽  
Rasim Gucalp ◽  
...  
Keyword(s):  
Phase Ii ◽  
Primary Endpoint ◽  
Performance Status ◽  
Progression Free Survival ◽  
Dose Schedule ◽  
Phase Iii ◽  
Smoking History ◽  
Clinical Activity ◽  
P Value ◽  
Randomized Phase Ii

8097 Background: Preclinical and phase I studies showed that PDS optimizes cytotoxicity of concurrent EGFR inhibitors and chemotherapy. We conducted a randomized phase II trial to assess relative efficacy of Pem alone (Arm A) versus Pem +Erl on a PDS dose-schedule (Arm B) as 2nd-line therapy in pts with advanced NSCLC (NCT00950365). Methods: Eligible pts were randomized 2:1 (Arm B: A), stratified by sex, smoking history, and performance status (0/1 vs 2). Accrual was restricted to non-squamous histology in 2009. Treatment: Arm A – Pem 500 mg/m2IV on day 1; Arm B – Pem + Erl 150 mg po QD on days 2-17. 1 cycle = 3 weeks. Primary endpoint was progression-free survival (PFS). 50 pts in Arm B were needed to detect an increase in median PFS from ~3 to 4.5 months. Results: 83 pts were entered. Age: 63 yo. Female: 42 (53%). Smoking ≥15PY: 58 (72%). Nonsquamous: 78 (99%). The primary endpoint of the study was met: Efficacy results from 79 eligible pts showed 1.6-fold longer PFS in Arm B (4.6 m) compared to Arm A (2.8 m). Although the study was not designed to directly compare two arms, p value was 0.052. Toxicity: G3/4 Hem (A/B): 8(30%)/12(23%); Neutropenia with infection (A/B): 0/3(6%). G3/4 Non-Hem (A/B): skin rash: 0/3(6%); diarrhea: 0/2(4%); joint pain: 1(4%)/6(11.5%). Treatment related death (A/B): 0/1. Interstitial lung disease (A/B): 0/1. Conclusions: PDS of Pem and Erl is well tolerated and has promising clinical activity in 2nd-line non-squamous NSCLC. Ongoing correlative studies aim to identify a subgroup of patients who might benefit most from this treatment, which will guide the design of a confirmatory phase III study. (UL1 RR024146, P30CA093373, Lilly, Astellas) Clinical trial information: NCT00950365. [Table: see text]

Randomized phase II study of 6 versus 12 months of adjuvant imatinib for patients with intermediate- or high-risk GIST.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 9-9
Author(s):  
Kazuya Muguruma ◽  
Yukinori Kurokawa ◽  
Toshimasa Tsujinaka ◽  
Junya Fujita ◽  
Takuya Nakai ◽  
...  
Keyword(s):  
High Risk ◽  
Phase Ii ◽  
Interim Analysis ◽  
Phase Ii Study ◽  
Hazard Ratio ◽  
P Value ◽  
Adjuvant Imatinib ◽  
Randomized Phase Ii ◽  
Ecog Ps

9 Background: The Z9001 study revealed adjuvant imatinib for 1 year significantly improved RFS in GIST patients (pts). The SSGXVIII study compared 3 years with 1 year of adjuvant imatinib for high risk GIST pts, but there was no study to evaluate shorter period of imatinib administration than 1 year. We conducted a randomized phase II study to compare 6 months (6-mo) with 12 months (12-mo) adjuvant imatinib for intermediate or high risk GIST pts. Methods: Inclusion criteria included ECOG-PS of 0 or 1, age between 20 and 79 years, and primary KIT-positive GIST with intermediate or high risk according to the Fletcher criteria. Pts were randomized assigned to the 6-mo or 12-mo treatment of imatinib 400 mg/day after complete resection. The primary endpoint was recurrence-free survival (RFS). The study was designed as a randomized screening trial to evaluate non-inferiority with margin of hazard ratio 1.67, 1-sided alpha 0.2 and power 0.8. Results: Ninety-two pts were randomly allocated the 6-mo group (n=45) or the 12-mo group (n=47) between Dec 2007 and Aug 2011, which was well balanced for baseline characteristics. One patient was ineligible due to non-GIST (desmoid) tumor at a central review. The proportions of pts completed their assigned adjuvant treatment were 80% in the 6-mo and 70% in the 12-mo group. The first interim analysis was conducted at Sep 2012 with the median follow-up time of 33 months. The 1- and 2-year RFS were 82% and 65% in the 6-mo group and 96% and 86% in the 12-mo group, respectively. Hazard ratio of recurrence was 1.81 (95%CI: 0.84-3.91), and the 2-sided log-rank p value was 0.12. Adjuvant imatinib was well tolerated, with one patient of Gr. 4 rash and no treatment-related death. Because of the lower efficacy of the 6-mo group than expected, the Data and Safety Monitoring Committee recommended the early release of first interim analysis results. Conclusions: Adjuvant Imatinib for 6-mo was inferior in efficacy to that for 12-mo in terms of RFS. Shortening of the adjuvant imatinib duration is not recommended for intermediate or high risk GIST pts. Clinical trial information: UMIN000000950.

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