Survival outcomes by tumor human papillomavirus (HPV) status in stage III-IV oropharyngeal cancer (OPC) in RTOG 0129

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6003-6003 ◽  
Author(s):  
M. L. Gillison ◽  
J. Harris ◽  
W. Westra ◽  
C. Chung ◽  
R. Jordan ◽  
...  

6003 Background: The favorable prognosis for HPV-positive (pos) OPC requires confirmation in a clinical trial of sufficient size to account for confounding variables including smoking. Methods: A correlative study was performed to evaluate the association of tumor HPV status (THS) and survival in a randomized phase 3 trial comparing standard fractionation (FX) radiotherapy (RT) and cisplatin (cis) (100 mg/m2, days 1, 22, 43) to accelerated FX-RT and cis (100 mg/m2, days 1, 22). THS for OPC cases was determined by HPV16 in situ hybridization (ISH). Two-year overall (OS, death) and progression-free survival (PFS, progression, salvage surgery, death) for patients with HPV-pos and HPV-negative [neg] OPC were estimated along with 95% confidence intervals (CIs) by Kaplan-Meier method and compared by log-rank test. Hazard ratios (HR) for OS/PFS comparing HPV-pos to HPV-neg OPC after adjustment for treatment assignment, age, race, T and N stage, and smoking (< or ≥ 20 pack-years [p-y]) were estimated by use of Cox models along with 95% CIs with multiple imputation for cases with undetermined THS and/or missing p-y. Results: THS was evaluable for 73% (317/433) of OPC cases and 60.6% (55.2–65.9) were HPV16-positive. OS/PFS outcomes were similar for cases with and without HPV determination. After median follow-up of 4.4 years, cases with HPV-pos OPC had better OS (p < 0.0001; 2-year 87.5% [82.8–92.2] vs 67.2% [58.9–75.4]) and PFS (p < 0.0001; 2-year 71.9% [65.5–78.2] vs 51.2% [42.4–59.9]). Patients with HPV-pos OPC had a 59% reduction in risk of death (HR 0.41 [0.27–0.64]) and a 46% reduction in risk of progression or death (HR 0.54 [0.37–0.78]). Results with and without imputation were consistent. The hazard of death was elevated for HPV-neg OPC with ≥ 20 p-y (HR 4.33), HPV-neg OPC with < 20 p-y (HR 2.41), and HPV-pos OPC with ≥ 20 p-y (HR 1.79), relative to HPV-pos OPC with <20 p-y. Second primary tumors were less common among HPV-pos cases and patterns of first failure were similar. Conclusions: Tumor HPV status is strongly associated with OS/PFS among OPC patients receiving standard of care chemo-radiation, and should now be a stratification factor for all clinical trials including OPC cases, and separate trials based on THS should be considered. No significant financial relationships to disclose.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 328-328 ◽  
Author(s):  
Lindsay Jennifer Andrew Rayner ◽  
Amarnath Challapalli ◽  
Eve Blackmore ◽  
Katherine Rea ◽  
Natasha Wells ◽  
...  

328 Background: Following CHAARTED & STAMPEDE, upfront Docetaxel chemotherapy became standard of care for metastatic hormone-naïve prostate cancer (mHNPC). We sought to evaluate our experience in the elderly group of patients (>70 yrs) compared with the non-elderly cohort. Methods: A retrospective analysis was undertaken of 38 patients commenced on upfront docetaxel chemotherapy, from Jan 16 - Jan 17. Patients were stratified as low (LR) and high risk (HR), as per the LATITUDE study. Progression was defined as per PCWG-3 criteria. The progression free survival (PFS) was calculated as time from start of treatment to date of progression and analysed by Kaplan-Meier estimates and log-rank test. Rates of febrile neutropenia (FN) were also evaluated. Results: The median age was 69 (range: 53-80) yrs, with 50% (19/38) HR patients. The median PFS was 11.5m for progressors (P; 42%) and not reached for non-progressors (NP; 58%), (p<0.0001). Granulocyte colony stimulating factor (G-CSF) was used in 13/38 (34%) patients; these did not experience FN. The overall rate of FN was 20% where G-CSF was not used. Overall 31/38 (81.6%) completed 6 cycles of chemotherapy, with 26% requiring dose reductions (Table). Overall, of the 9/16 (56.3%) patients who progressed within 6m of completing docetaxel, 3 had Cabazitaxel as the next treatment (P: 2/3 (66.7%), median PFS 6.2m) and 6 had novel androgen receptor targeted therapy (P: 5/6 (83.3%), median PFS 3.3m). Conclusions: Upfront docetaxel is reasonably well tolerated in the elderly with comparable median PFS to younger patients. Use of GCSF significantly minimizes the risk of FN in this group and should be considered as standard of care. In patients who progress within 6m of completing docetaxel, we feel optimal sequencing to be Cabazitaxel followed by subsequent therapies.[Table: see text]


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e13006-e13006
Author(s):  
Dory Abou-Jaoude ◽  
Joseph A Moore ◽  
Matthew B Moore ◽  
Philip Twumasi-Ankrah ◽  
Elizabeth Ablah ◽  
...  

e13006 Background: The 5-year survival for patients (pts) with glioblastoma (GBM) is low at approximately 3%. Radiotherapy plus concomitant and adjuvant temozolomide (TMZ) remain the standard of care. The optimal duration of therapy with TMZ is unknown, though treatment periods of 6 months (mo), 12 mo and longer have been utilized. Whether or not there is a benefit with longer treatment duration is controversial. Methods: A retrospective chart review of all pts diagnosed with GBM who were treated at a regional referral center was conducted with data obtained from their electronic medical records. These pts were treated with TMZ for up to 2 years between January 1, 2002 and December 31, 2011. Survival was calculated as the time from initial surgical diagnosis until death. The Kaplan-Meier method with log-rank test was used to estimate the progression-free survival (PFS) as well as the overall survival (OS) distribution of pts after treatment. The results were compared to historical controls and data from previous clinical trials of pts treated up to 1 year. Results: Data from 56 pts were evaluated, the majority of whom had gross total resection and had external pathology review confirming the diagnosis of GBM. The OS probability was 55.4% (SE = 0.068) at 1 year, 26.9% (SE = 0.067) at 2 years and 20.1% (SE = 0.065) at 3 years. The median PFS time in this study group was 8 mo (95% CI = 4.0 – 9.0 mo). The probability of no progression at 2 years was 8.6% (SE = 0.05). Seven pts (12.5%) were treated with TMZ for 2 years. The probability of disease progression at 2 years among these pts was 33.3% with a median time-to-progression of 20 mo (95% CI = 5.0-28.0). These patients showed an increased survival probability at 3 years compared to pts who did not receive the 2 year treatment of TMZ (log-rank test Chi-square = 12.4, p = 0.0004). Conclusions: This analysis suggests that there may be an advantage for a longer duration of TMZ therapy in pts with GBM. In this review, treatment with TMZ for 2 years was associated with an increased survival benefit. While we consider the sample size to be too small for generalization, a prospective/multicenter study with a larger sample size might better evaluate the question of duration of TMZ therapy, particularly if both clinical and basic science data are paired.


2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 142-142
Author(s):  
Charles J. Ryan ◽  
Matthew Raymond Smith ◽  
Karim Fizazi ◽  
Fred Saad ◽  
Cora N. Sternberg ◽  
...  

142 Background: AA + prednisone (P) significantly increased OS, time to opiate use, and was well tolerated at the COU-AA-302 final analysis. Here we further characterize OS benefit adjusting for crossover therapy and for baseline prognostic factors. Methods: Patients (N = 1,088) were randomized 1:1 to receive AA (1 g) + P (5 mg po BID) vs P. Co-primary end points were radiographic progression-free survival and OS. Median time to events with 95% CI was estimated using the Kaplan-Meier method. Stratified log-rank test was used to test the difference in treatment effect. Adjustment for crossover utilized the iterative parameter estimate (IPE) and impact of baseline prognostic factors was examined via the multivariate Cox proportional hazard model. Results: With a median follow-up of 49.2 months and 741 deaths (96% of required), AA + P significantly reduced the risk of death vs P (19%) and prolonged median OS (34.7 vs 30.3 months) (Table). 44% of patients initially receiving P alone subsequently received AA + P as crossover per protocol (17%) or as subsequent therapy (27%). IPE adjustment resulted in a 26% reduction in the risk of death (Table). By multivariate analysis, AA + P treatment led to a 21% reduction in the risk of death; baseline prostate-specific antigen (PSA), lactate dehydrogenase (LDH), hemoglobin, alkaline phosphatase (ALP), bone metastases, and age were significant OS prognostic factors (Table). Conclusions: AA + P yielded a statistically significant improvement in OS. Greater improvement in OS was observed after adjusting for the 44% of patients originally on P who ultimately received AA + P. Adjusting for baseline prognostic factors also demonstrated an AA + P OS benefit. Clinical trial information: NCT00887198. [Table: see text]


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 8526-8526 ◽  
Author(s):  
Jhanelle Elaine Gray ◽  
Augusto E. Villegas ◽  
Davey B. Daniel ◽  
David Vicente ◽  
Shuji Murakami ◽  
...  

8526 Background: In the phase 3 PACIFIC study of patients with unresectable, Stage III NSCLC without progression after chemoradiotherapy (CRT), durvalumab demonstrated significant improvements versus placebo in the primary endpoints of progression-free survival (HR, 0.52; 95% CI, 0.42–65; P < 0.0001) and overall survival (OS; HR, 0.68; 95% CI, 0.53–0.87; P = 0.00251). Safety was similar and durvalumab had no detrimental effect on patient-reported outcomes. Here, we report 3-year OS rates for all patients randomized in the PACIFIC study. Methods: Patients with WHO PS 0/1 (any tumor PD-L1 status) who received ≥2 cycles of platinum-based CRT were randomized (2:1), 1–42 days following CRT, to receive durvalumab 10 mg/kg intravenously every 2 weeks or placebo, up to 12 months, and stratified by age, sex, and smoking history. OS was analyzed using a stratified log-rank test in the ITT population. Medians and OS rates at 12, 24 and 36 months were estimated by Kaplan-Meier method. Results: In total, 713 patients were randomized of whom 709 received treatment (durvalumab, n = 473; placebo, n = 236). The last patient had completed the protocol-defined 12 months of study treatment in May 2017. As of January 31, 2019 (data cutoff), 48.2% of patients had died (44.1% and 56.5% in the durvalumab and placebo groups, respectively). The median duration of follow-up was 33.3 months (range, 0.2–51.3). Updated OS remained consistent with that previously reported (stratified HR 0.69, 95% CI, 0.55–0.86), with the median not reached (NR; 95% CI, 38.4 months–NR) with durvalumab versus 29.1 months (95% CI, 22.1–35.1) with placebo. The 12-, 24- and 36-month OS rates with durvalumab and placebo were 83.1% versus 74.6%, 66.3% versus 55.3%, and 57.0% versus 43.5%, respectively. After discontinuation, 43.3% and 57.8% in the durvalumab and placebo groups, respectively, received subsequent anticancer therapy (9.7% and 26.6% subsequently received immunotherapy). OS subgroup results will be presented. Conclusions: Updated OS data from PACIFIC, including 3-year survival rates, underscore the long-term clinical benefit with durvalumab following CRT and further establish the PACIFIC regimen as the standard of care in this population. Clinical trial information: NCT02125461.


2019 ◽  
Vol 12 (3) ◽  
pp. 65-69 ◽  
Author(s):  
Dory Abou Jaoude ◽  
Joseph A Moore ◽  
Matthew B Moore ◽  
Philip Twumasi-Ankrah ◽  
Elizabeth Ablah ◽  
...  

Introduction The five-year survival rate for patients with glioblastoma (GBM) is low at approximately 4.7%. Radiotherapy plus concomitant and adjuvant temozolomide (TMZ) remains the standard of care. The optimal duration of therapy with TMZ is unknown. This study sought to evaluate the survival benefit of two years of treatment. Methods This was a retrospective chart review of all patients diagnosed with GBM and treated with TMZ for up to two years between January 1, 2002 and December 31, 2011. The Kaplan-Meier method with log-rank test was used to estimate the progression-free survival (PFS) and the overall survival (OS). The results were compared to historical controls and data from previous clinical trials of patients treated up to one year. Results Data from 56 patients with confirmed GBM were evaluated. The OS probability was 54% (SE = 0.068) at one year, 28.3% (SE = 0.064) at two years, 17.8% (SE = 0.059) at three years, and 4% (SE = 0.041) at five years. Seven patients (12.5%) were treated with TMZ for two years. Their median time-to-progression was 28 months (95% CI = 5.0 - 28.0), and they had an increased survival probability at three years compared to other patients (log-rank test χ2 (1, N = 56) = 19.2, p < 0.0001). Conclusions There may be an advantage for a longer duration of TMZ therapy among patients with GBM, but the sample size was too small for generalization. A multicenter prospective study is needed to dentify optimal duration of TMZ therapy.


2019 ◽  
Vol 65 (3) ◽  
pp. 321-329
Author(s):  
David Zaridze ◽  
Anush Mukeriya

Smoking not only increases the risk of the development of malignant tumors (MT), but affects the disease prognosis, mortality and survivability of cancer patients. The link between the smoking of cancer patients and increased risk of death by all diseases and oncological causes has been established. Mortality increases with the growth of the smoking intensity, i.e. the number of cigarettes, smoked per day. Smoking is associated with the worst general and oncological survivability. The statistically trend-line between the smoking intensity and survivability was observed: each additional unit of cigarette consumption (pack/year) leads to the Overall Survival Reduction by 1% (p = 0.002). The link between smoking and the risk of developing second primary tumors has been confirmed. Smoking increases the likelihood of side effects of the antitumor therapy both drug therapy and radiation therapy and reduces the treatment efficacy. The smoking cessation leads to a significant improvement in the prognosis of a cancer patient. Scientific data on the negative effect of smoking on the prognosis of cancer patients have a major clinical importance. The treatment program for cancer patients should include science-based methods for the smoking cessation. The latter is fundamentally important, taking into account that the smoking frequency among cancer patients is much higher than in the population.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8511-8511
Author(s):  
David R. Spigel ◽  
Corinne Faivre-Finn ◽  
Jhanelle Elaine Gray ◽  
David Vicente ◽  
David Planchard ◽  
...  

8511 Background: In the placebo-controlled Phase III PACIFIC trial of patients with unresectable Stage III NSCLC whose disease had not progressed after platinum-based concurrent chemoradiotherapy (cCRT), durvalumab improved overall survival (OS) (stratified hazard ratio [HR] 0.68; 95% confidence interval [CI] 0.53–0.87; p=0.0025; data cutoff [DCO] Mar 22, 2018) and progression-free survival (PFS) (stratified HR 0.52, 95% CI 0.42–0.65; p<0.0001; DCO Feb 13, 2017) based on the DCOs used for the primary analyses, and the degree of benefit remained consistent in subsequent updates. Durvalumab was associated with a manageable safety profile, and did not detrimentally affect patient-reported outcomes, compared with placebo. These findings established consolidation durvalumab after CRT (the ‘PACIFIC regimen’) as the standard of care in this setting. We report updated, exploratory analyses of OS and PFS, assessed approximately 5 years after the last patient was randomized. Methods: Patients with WHO PS 0/1 (and any tumor PD-L1 status) whose disease did not progress after cCRT (≥2 overlapping cycles) were randomized (2:1) 1–42 days following cCRT (total prescription radiotherapy dose typically 60–66 Gy in 30–33 fractions) to receive 12 months’ durvalumab (10 mg/kg IV every 2 weeks) or placebo, stratified by age (<65 vs ≥65 years), sex, and smoking history (current/former smoker vs never smoked). The primary endpoints were OS and PFS (blinded independent central review; RECIST v1.1) in the intent-to-treat (ITT) population. HRs and 95% CIs were estimated using stratified log-rank tests in the ITT population. Medians and OS/PFS rates at 60 months were estimated with the Kaplan–Meier method. Results: Overall, 709/713 randomized patients received treatment in either the durvalumab (n/N=473/476) or placebo (n/N=236/237) arms. The last patient had completed study treatment in May 2017. As of Jan 11, 2021 (median follow-up duration of 34.2 months in all patients; range, 0.2–74.7 months), updated OS (stratified HR 0.72, 95% CI 0.59–0.89; median 47.5 vs 29.1 months) and PFS (stratified HR 0.55, 95% CI 0.45–0.68; median 16.9 vs 5.6 months) remained consistent with the results from the primary analyses. The 60-month OS rates were 42.9% and 33.4% with durvalumab and placebo, respectively, and 60-month PFS rates were 33.1% and 19.0%, respectively. Updated treatment effect estimates for patient subgroups will be presented. Conclusions: These updated survival analyses, based on 5-year data from PACIFIC, demonstrate robust and sustained OS plus durable PFS benefit with the PACIFIC regimen. An estimated 42.9% of patients randomized to durvalumab remain alive at 5 years and approximately a third remain both alive and free of disease progression. Clinical trial information: NCT02125461.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16567-e16567
Author(s):  
Anish B. Parikh ◽  
Sarah P. Psutka ◽  
Yuanquan Yang ◽  
Katharine Collier ◽  
Abdul Miah ◽  
...  

e16567 Background: ICI/TKI combinations are a new standard of care for the initial treatment (tx) of mRCC. Efficacy and toxicity of such combination regimens beyond the first-line (1L) setting remain unknown. Methods: We retrospectively reviewed charts for adult patients (pts) receiving an ICI/TKI combination in any line of tx for mRCC of any histology at one of two academic centers as of May 1, 2020. ICIs included pembrolizumab (Pm), nivolumab (Ni), ipilimumab (Ip), or avelumab (Av); TKIs included sunitinib (Su), axitinib (Ax), pazopanib (Pz), lenvatinib (Ln), or cabozantinib (Ca). Clinical data including pt demographics, histology, International mRCC Database Consortium (IMDC) risk group, tx history, and ICI/TKI tx and toxicity details were recorded. Outcomes included objective response rate (ORR), median progression-free survival (mPFS), and safety, analyzed via descriptive statistics and the Kaplan-Meier method. Results: Of 85 pts, 69 (81%) were male and 67 (79%) had clear cell histology. IMDC risk was favorable (24%), intermediate (54%), poor (20%), and unknown (2%). 39% had ICI/TKI tx in the 1L setting. ICI/TKI regimens included Pm/Ax (33%), Ni/Ca (25%), Ni/Ax (20%), Av/Ax (11%), Ni/Ip/Ca (8%), Ni/Su (2%), and Ni/Ln (1%). ORR and mPFS stratified by line of tx and prior tx are shown in the table. Of 52 pts who received ICI/TKI tx as salvage (after 1L), 52% had a grade 3 or higher (≥G3) adverse event (AE), of which the most common were anorexia (13.5%), diarrhea and hypertension (11.5% each), and fatigue (9.6%). 65% of pts on salvage ICI/TKI tx stopped tx for progression/death, while 16% stopped tx for ≥G3 AE. ≥G3 AE rates by line of tx were 62.5% (2L), 50% (3L), and 45% (≥4L). Conclusions: ICI/TKI combination therapy is effective and safe beyond the 1L setting. Prior tx history appears to impact efficacy but has less of an effect on safety/tolerability. These observations will need to be confirmed in prospective studies.[Table: see text]


2021 ◽  
pp. postgradmedj-2021-139981
Author(s):  
Shimin Tang ◽  
Hao Jiang ◽  
Zhijun Cao ◽  
Qiang Zhou

IntroductionProstate cancer is a common malignancy in men that is difficult to treat and carries a high risk of death. miR-219-5p is expressed in reduced amounts in many malignancies. However, the prognostic value of miR-219-5p for patients with prostate cancer remains unclear.MethodsWe retrospectively analysed data from 213 prostate cancer patients from 10 June 2012 to 9 May 2015. Overall survival was assessed by Kaplan-Meier analysis and Cox regression models. Besides, a prediction model was constructed, and calibration curves evaluated the model’s accuracy.ResultsOf the 213 patients, a total of 72 (33.8%) died and the median survival time was 60.0 months. We found by multifactorial analysis that miR-219-5p deficiency increased the risk of death by nearly fourfold (HR: 3.86, 95% CI): 2.01 to 7.44, p<0.001) and the risk of progression by twofold (HR: 2.79, 95% CI: 1.68 to 4.64, p<0.001). To quantify each covariate’s weight on prognosis, we screened variables by cox model to construct a predictive model. The Nomogram showed excellent accuracy in estimating death’s risk, with a corrected C-index of 0.778.ConclusionsmiR-219-5p can be used as a biomarker to predict death risk in prostate cancer patients. The mortality risk prediction model constructed based on miR-219-5p has good consistency and validity in assessing patient prognosis.


2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii55-ii55
Author(s):  
M J Sousa ◽  
J Magalhães ◽  
R Basto ◽  
C Costa ◽  
A Pego ◽  
...  

Abstract BACKGROUND Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumour in adults. The current standard of care for newly diagnosed GBM is maximal surgical resection, followed by radiotherapy plus concomitant and adjuvant temozolomide (TMZ). This study aimed to evaluate the survival outcomes and identify predictors of survival among these patients. MATERIAL AND METHODS We performed a single-centre retrospective analysis of GBM patients treated with radiotherapy plus concomitant and adjuvant TMZ from 2013 to 2020. The analyses of progression-free survival (PFS) and overall survival (OS), each one evaluated starting from initial diagnosis, were performed. Survival curves were estimated with the Kaplan- Meier method and compared using the log-rank test. RESULTS Fifty-eight patients were identified. The median age was 61 years (range 18- 80), 51 (88%) patients were in ECOG-PS 0–1, 6 (10%) patients had isocitrate dehydrogenase (IDH) mutation and 53 (91%) of patients had undergone debulking surgery. At a median follow-up of 21 months, median OS was 12.8 months (95% confidence interval [CI] 9.7–15.9), whereas median PFS was 9.5 months (95% CI 8.5–10.5). The 1-year survival rate was 42% and the 2-year survival rate was 10%. Grade 3 or 4 hematologic toxicity occurred in 11 (19%) patients. Twenty-five (42%) patients completed at least 6 cycles of TMZ monotherapy with statistically significant differences between this sub-group and those who weren’t able to continue TMZ monotherapy [median OS 19.3 months (95% CI 14.4–24.2) vs 10.6 months (95% CI 7.8–13.4) p&lt;0.001]. ECOG-PS = 0 [median OS 16.7 months (95% CI 13.4–20.0, p=0.001)] and patients under 65 years of age [median OS 15.6 months (95% CI 12.3–18.9, p=0.02) were associated with significantly better median OS. CONCLUSION The current standard of care treatment for GBM remains poor. An important factor predictor of survival is the completion of the 6 maintenance cycles of TMZ. At baseline, ECOG PS and the patient’s age could be used to define patient prognosis.


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