A phase I trial of concurrent chemoradiotherapy (cCRT) with the conventional administration of docetaxel (D) and cisplatin (P) for dry-stage III non-small cell lung cancer (NSCLC) (JCOG9901DI)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7549-7549
Author(s):  
N. Hida ◽  
S. Tsujimura ◽  
T. Fujii ◽  
K. Naoki ◽  
H. Kunikane ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Trial ◽  
Performance Status ◽  
Objective Response ◽  
Locally Advanced ◽  
Recommended Dose ◽  
Stage Iii ◽  
Ecog Performance Status ◽  
Full Dose ◽  
Level 2

7549 Background: In cCRT for locally advanced NSCLC, full dose chemotherapy with a new agent plus a platinum doublet is considered to have unacceptable toxicities. Consequently, weekly or split chemotherapy doses are often used. However, cCRT plus conventional regimens are expected to enhance systemic effects. This phase I trial aimed to establish the MTD of cCRT plus conventional administration of DP (conv-DP). Methods: Unresectable stage III NSCLC patients (pts) (<70 years) with ECOG performance status 0–1 and adequate organ function were eligible. Pts received 60 Gy in 30 fractions by once daily radiotherapy. Concurrent P (day1; 60 mg/m2 at levels 1–3, 80 mg/m2 at level 4) and D (day1; 30 mg/m2 at level 1, 40 mg/m2 at level 2, 50 mg/m2 at levels 3–4) were given every 4 weeks for at least 2, and up to 4 courses. DLT was defined as either Gr3/4 febrile neutropenia, Gr4 neutropenia lasting ≥ 4 days, Gr4 thrombocytopenia, Gr2 pneumonitis or any Gr3 non-hematological toxicities except for nausea, vomiting and alopecia. Results: Eighteen pts were enrolled from 06/1999 to 05/2006: 6 pts at levels 2 and 4, 3 pts at levels 1 and 4; 13 males; median age 60 years (range 43–70); stage IIIA/IIIB 5/13; histology Ad/Sq/Large 9/7/2. DLTs were observed for 3 pts at level 2 (D40/P60): Gr4 pneumonitis at level 3(D50/P60), Gr3 cerebral infarction and Gr3 atrial fibrillation. Although 3 cases were added at these levels, tolerability for each level was cleared, as DLTs occurred for ≤ 2 pts among 6. MTD was not detected, even at the highest dose (D50/P80). However, dose escalation was stopped, as D60/P80 was the recommended dose for chemotherapy alone in Japan. Radiotherapy (60 Gy) was completed for 15 pts. Seventeen pts received more than 2 courses of chemotherapy. No Gr3/4 esophagitis or severe hematologic toxicities were observed. Objective response rate was 89% and 1-yr survival rate was 55%. Conclusions: The recommended dose in this regimen was D50/P80, which was near the full dose for conv-DP. Based on these promising results, we are planning a phase II trial to evaluate the efficacy and toxicity of this cCRT with conv-DP therapy. No significant financial relationships to disclose.

Phase I trial of docetaxel (D) plus samarium153 (Sm 153) in patients (pts) with hormone refractory prostate cancer (HRPC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15547-15547 ◽  
Author(s):  
V. J. Sinibaldi ◽  
M. A. Carducci ◽  
T. DeWeese ◽  
J. Weber ◽  
R. Drew ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Phase I ◽  
Phase I Trial ◽  
Performance Status ◽  
Hepatic Function ◽  
Great Promise ◽  
Significant Activity ◽  
Ecog Performance Status ◽  
Preclinical Data ◽  
Hormone Refractory

15547 Background: Bone targeted approaches hold great promise for improving outcomes in HRPC. Docetaxel (D) and samarium 153 (Sm153 ) have individually demonstrated a clinical benefit and preclinical data strongly support biological synergism in HRPC. Preclinical data suggests that 24 hour after a dose of D, there is maximum G2M arrest. This results in the accumulation of cells in the most radiosensitive phase of the cell cycle. This phase I trial was designed to evaluate toxicity and preliminary efficacy of combined D and Sm153 administered sequentially in advanced HRPC. Methods: HRPC pts progressing after anti-androgen withdrawal; = 2 prior chemotherapy regimens; acceptable bone marrow, renal and hepatic function were eligible. Planned D treatment in 4 cohorts (N=3/cohort) includes: Cohort 1: D 50mg/m2 IV on days 1, 22, 91, and 112; cohort 2: D 75mg/m2 IV on days 1 and 22 followed by 50mg/m2 IV on days 91 and 112; cohort 3: D 75mg/m2 IV on days 1 and 22 followed by 75mg/m2 IV on days 91 and 112; cohort 4: D 75 mg/m2 IV on days 1, 22, 42, 91, 112, and 133. Sm 153 (1.0 mi/Kg) is administered IV days 2 and 92 of each cycle. Cycles are repeated Q 12 wks (max 2 cycles). The endpoint for this trial is dose limiting toxicity and maximal tolerated dose. Results: From 5/11/05 - 1/7/07 ten pts were enrolled. Median: age 69.5 yrs (range 58–76), ECOG performance status 1 (range 0–1), baseline PSA 76.65 ng/ml (range 9.6–1064 ng/ml ), prior hormonal manipulations 3 (range1–6). Three pts had prior taxotere and 3 pts had prior palliative RT. All had bone metastases and 2 also had soft tissue disease. Five pts completed 2 cycles of treatment as planned. Five pts had 1 cycle (one pt is on treatment, 3 pts had PD and 1 had prolonged grade 1 thrombocytopenia =3 wks). Nine of 10 pts had reversible grade 3 / 4 neutropenia (1 pt had reversible episode of neutropenia with fever). Seven of 7 symptomatic pts had improvement in pain. Four of 10 of pts had a 50 % decline in PSA level lasting = 4 weeks; no soft tissue disease responses. Conclusions: Our preliminary data suggest that Q 3 wk D and Q 3 month Sm153 may be administered simultaneously at full doses in extensively pretreated HRPC pts, with acceptable toxicity and significant activity. This study is supported by a grant from sanofi- aventis and Sm153 is provided by Cytogen. No significant financial relationships to disclose.

PACIFIC-2: Phase 3 study of concurrent durvalumab and platinum-based chemoradiotherapy in patients with unresectable, stage III NSCLC.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS8573-TPS8573 ◽  
Author(s):  
Jeffrey D. Bradley ◽  
Makoto Nishio ◽  
Isamu Okamoto ◽  
Michael David Newton ◽  
Leonardo Trani ◽  
...  
Keyword(s):  
Performance Status ◽  
Objective Response ◽  
Additional Benefit ◽  
Stage Iii ◽  
Phase 3 ◽  
Ecog Performance Status ◽  
Double Blind ◽  
Unresectable Stage ◽  
Stage Iii Nsclc ◽  
To Receive

TPS8573 Background: Durvalumab, a selective, high-affinity, engineered human IgG1 mAb that blocks PD-L1 binding to PD-1 and CD80, is approved in the US, Japan and several other countries, for the treatment of patients (pts) with unresectable, stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent chemoradiotherapy (cCRT). These approvals were based on results from the phase 3 PACIFIC study, in which durvalumab was given 1–42 days after completion of definitive cCRT and significantly improved progression-free survival (PFS) vs placebo (median 16.8 vs 5.6 months; HR 0.52, 95% CI 0.42– 0.65; p<0.001) and overall survival (OS) vs placebo (stratified HR 0.68; 99.73% CI 0.47–0.997; p=0.0025). Increasing evidence suggests additional benefit when anti-PD-1/PD-L1 therapies are administered alongside cCRT. The PACIFIC 2 study therefore aims to assess whether durvalumab plus cCRT provides additional benefit, in terms of PFS and objective response rate (ORR), compared with cCRT alone. Methods: PACIFIC 2 is a phase 3, randomized, double-blind, placebo-controlled, multicenter, international study. Approximately 300 pts with unresectable stage III NSCLC will be randomized (2:1) to receive either durvalumab (intravenous 1500 mg) every 4 weeks (q4w) + cCRT, or placebo q4w + cCRT. Eligible pts must have histologically or cytologically confirmed stage III disease; ECOG performance status 0 or 1; and life expectancy >12 weeks at randomization. Pts who discontinue treatment will be followed for safety and OS. Primary endpoints are PFS and ORR (RECIST v1.1) assessed via blinded independent central review. Secondary endpoints include OS; OS at month 24; complete response (CR) rate; duration of response; disease control rate; time to death/distant metastases; time from randomization to second progression; safety; and symptoms, functioning and global health status. Pts with a CR, partial response or stable disease will continue to receive durvalumab or placebo until clinical or RECIST v1.1-defined disease progression, or until another discontinuation criterion is met. Study enrollment began in March 2018 and recruitment is ongoing. Clinical trial information: NCT03519971.

scholarly journals Confirmed Activity and Tolerability of Weekly Paclitaxel in the Treatment of Advanced Angiosarcoma

Sarcoma ◽  
2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Gaetano Apice ◽  
Antonio Pizzolorusso ◽  
Massimo Di Maio ◽  
Giovanni Grignani ◽  
Vittorio Gebbia ◽  
...  
Keyword(s):  
Performance Status ◽  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Multicenter Trial ◽  
Weekly Paclitaxel ◽  
Ecog Performance Status ◽  
Small Series ◽  
Prospective Phase ◽  
Pretreated Patients

Background.In several prospective and retrospective studies, weekly paclitaxel showed promising activity in patients with angiosarcoma.Patients and Methods. Our study was originally designed as a prospective, phase II multicenter trial for patients younger than 75, with ECOG performance status 0–2, affected by locally advanced or metastatic angiosarcoma. Patients received paclitaxel 80 mg/m2intravenously, at days 1, 8, and 15 every 4 weeks, until disease progression or unacceptable toxicity. Primary endpoint was objective response.Results. Eight patients were enrolled but, due to very slow accrual, the trial was prematurely stopped and further 10 patients were retrospectively included in the analysis. Out of 17 evaluable patients, 6 patients obtained an objective response (5 partial, 1 complete), with an objective response rate of 35% (95% confidence interval 17%–59%). Of note, five responses were obtained in pretreated patients. In the paper, details of overall survival, progression-free survival, and tolerability are reported.Conclusions. In this small series of patients with locally advanced or metastatic angiosarcoma, weekly paclitaxel was confirmed to be well tolerated and active even in pretreated patients.

A phase I trial of bexarotene and docetaxel in patients with advanced solid tumors

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13085-13085
Author(s):  
M. J. Pishvaian ◽  
K. Firozvi ◽  
J. J. Hwang ◽  
J. L. Marshall ◽  
P. Ramzi ◽  
...  
Keyword(s):  
Phase I ◽  
Solid Tumors ◽  
Phase I Trial ◽  
Performance Status ◽  
Fixed Dose ◽  
Ecog Performance Status ◽  
Radiation Recall ◽  
Serum Triglycerides ◽  
Experienced Grade ◽  
Grade Iii

13085 Background: Retinoids have been used to treat a wide variety of malignancies. Bexarotene is a synthetic retinoid that binds preferentially to the RXR subclass of retinoid receptors. In the initial phase I trial of bexarotene, a subset of patients with non-small cell lung cancer (NSCLC) had prolonged stabilization of disease and survival. In vitro evidence suggests that the effects of retinoids may be enhanced when used in conjunction with taxanes. This is a phase I trial designed to determine the maximum tolerated dose of docetaxel in combination with a fixed dose of bexarotene. Methods: Patients with pathologically confirmed solid tumors for whom no standard therapies exist, who have an ECOG performance status ≤2, adequate organ function and normal serum triglycerides were eligible. Each cycle was 4 weeks long. Oral bexarotene was given at 400 mg/m2 daily. Docetaxel was given weekly for 3 out of 4 weeks at two dose levels, 25 or 30 mg/m2, for up to 6 cycles. For patients exhibiting disease stabilization or response, treatment with bexarotene was continued until disease progression. Restaging studies were performed after every 2 cycles. Results: To date 10 patients have been enrolled, half of whom had NSCLC - 7 male, mean age = 61 (range 37–73), 100% PS = 0 or 1. 29 cycles were completed (range 1 to 8). 7 patients have been treated at 25 mg/m2 and 3 at 30 mg/m2 of docetaxel. Hypothyroidism, hypertriglyceridemia, and fatigue were common but generally mild. Two patients experienced grade III fatigue, and 1 each experienced grade III hypertriglyceridemia, neutropenia, and cough. There were no grade IV toxicities. Two patients were taken off study because of non-fatal radiation recall pneumonitis that was controlled with steroids. In this heavily pretreated population, of 8 patients assessable for response, 5 had stable disease for at least 2 cycles. One patient with NSCLC had a partial response that persisted for 6 cycles. Conclusions: Bexarotene and docetaxel (at a minimum of 25 mg/m2) can be safely coadministered. Care should be taken in patients who have been previously irradiated. Enrolment and dose escalation for the phase I trial is still ongoing. A phase II trial of the combination as second line therapy in NSCLC is planned. [Table: see text]

Phase I/II trial of doranidazole (PR-350) and concurrent thoracic radiotherapy (TRT) in patients (pts) with locally advanced (LA) non-small cell lung cancer (NSCLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17064-17064
Author(s):  
K. Takeda ◽  
S. Negoro ◽  
K. Nakagawa ◽  
Y. Segawa ◽  
Y. Nishimura ◽  
...  
Keyword(s):  
Phase I ◽  
Induction Chemotherapy ◽  
Performance Status ◽  
Locally Advanced ◽  
Cumulative Effect ◽  
Hypoxic Cell ◽  
Severe Toxicity ◽  
Ecog Performance Status ◽  
Prior Therapy ◽  
The Times

17064 Background: PR-350 was a nitoroimidazole derivative as a hypoxic cell radiosensitizer with low toxixity, developed by POLA Chemical Industries Inc.(Yokohama, Japan). We undertook this phase I/II trial to characterize the safety, pharmacokinetics (PK), and antitumor activity of the combination chemotherapy of platinum agent and paclitaxel followed by PR-350 and concurrent TRT in pts with LANSCLC. This trial was conducted by West Japan Thoracic Oncology Group (WJTOG). Methods: Major eligibility included 20–74 years old, histologically or cytologically proven NSCLC, surgically unresectable stage IIIA and IIIB, no prior therapy, ECOG performance status of 0 to 1, and adequate organ functions. All pts received two cycles of cisplatin of 80 mg/m2 and paclitaxel of 180 mg/m2 before radiotherapy with PR-350. The radiation dose was 60 Gy in 30 fractions of 2 Gy over 6 weeks. PR-350 dose of 2000 mg/m2 was administered as a 25 minutes intravenously prior to irradiation daily. The starting consecutive days were 10 times with daily TRT, and the times were escalated in increments of 10 times for successive groups of 6 new pts. PK studies of PR-350 were performed on the first day and the end. Induction chemotherapy of carboplatin (AUC = 6) and paclitaxel (200mg/m2) was also permitted in phase II portion. Results: 37 pts were enrolled into this trial. Major severe toxicity was radiation pneumonitis, which developed 2 treatment related deaths (TRD). Grade 3 or more esophagitis was not developed in this trial. PR-350 was able to administered 30 consecutive days with concurrent TRT. Overall response rate was 67.6% (95% CI: 50.2–82.0%). Median survival time was 16.8 months (95% CI: 12.1–21.9 months), and 1 and 2 year survival rate were 64% and 21%, respectively. No cumulative effect was demonstrated among 3 dose levels by PK studies. Conclusions: Induction chemotherapy followed by TRT with 30 times of PR-350 was well tolerated and promising for the treatment of LANSCLC. [Table: see text] No significant financial relationships to disclose.

A non-comparative phase II study of bendamustine hydrochloride in patients with pretreated soft tissue sarcoma (German Sarcoma Group-AIO 001)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 9525-9525
Author(s):  
F. Mayer ◽  
J. Schleicher ◽  
J. Huober ◽  
I. Meisinger ◽  
J. Pintoffl ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Response Rate ◽  
Performance Status ◽  
Objective Response ◽  
Locally Advanced ◽  
Ecog Performance Status ◽  
Adult Type ◽  
Efficacy Analysis ◽  
Clinically Significant

9525 Background: To assess the efficacy and safety of bendamustine hydrochloride, a nucleoside analogue with alkylating activity, in patients with adult type soft tissue sarcoma (STS) who have failed anthracyline-based chemotherapy. Methods: Pts with a ECOG performance status 0–2, measurable disease and adequate organ functions were eligible. All patients had inoperable locally advanced or metastatic disease and had progressive disease during or after first-line chemotherapy prior to study entry. Bendamustine was administered at a dose of 100 mg/sqm on day 1 and 2 every four weeks for a maximum of 6 cycles with tumour assessment every two cycles. The primary endpoint was overall response rate as defined by RECIST. The secondary endpoint was toxicity. A two-stage design was used (1st step: 14 pts, at least 1 PR in order to succeed with 2nd step; p0 = 5%, p1 = 25%, alpha = beta = 0.1). Results: 32 patients, median age 56 yrs (range, 18–74) with STS were recruited (3 pts not evaluable for efficacy analysis). In general the drug was well tolerated. Grade 3 toxicity was granulocytopenia in 9% and febrile neutropenia/fever in 3% of pts. No toxic death was seen in a total of 89 cycles administered. A single pt experienced a clinically significant allergic reaction (3%). Anti-tumour activity: 1 confirmed partial response (3%). A further 10 patients had progression arrest by cycle two (34%). Conclusions: The confirmed objective response rate is low. However, the incidence of progression arrest in pretreated adult type STS is in the range of other agents considered active in STS. The observed toxicity profile is favorable. Further investigation in STS appears warranted. No significant financial relationships to disclose.

Phase I trial of combination becatecarin and oxaliplatin in patients with advanced solid tumors

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2561-2561
Author(s):  
S. Manda ◽  
C. Mauser ◽  
J. Bokar ◽  
M. Cooney ◽  
J. Brell ◽  
...  
Keyword(s):  
Phase I ◽  
Solid Tumors ◽  
Dose Level ◽  
Phase Ii ◽  
Phase I Trial ◽  
Performance Status ◽  
Advanced Solid Tumors ◽  
Phase Ii Studies ◽  
Grade 3 ◽  
Level 2

2561 Background: Becatecarin (rebeccamycin analogue-RA) is an anti-tumor antibiotic with inhibitory activity against both topoisomerase II and I as well as DNA intercalating properties. We performed a phase I trial to a) determine the maximum tolerated dose (MTD) of RA in combination with oxaliplatin; b) determine the dose limiting toxicities (DLT) (c) obtain data on pharmacokinetics and (d) observe for any antitumor activity. Methods: Eligibility criteria included patients with advanced solid tumors refractory to standard therapy; performance status 0–2; adequate hematologic, renal and liver function. Patients were treated with RA as a 1 hour infusion daily x 5 and oxaliplatin on day 5 only, after RA infusion. Treatment was repeated q 21 days. The following dose levels were evaluated: Dose level 1: RA 80 mg/m2/d and oxaliplatin 90 mg/m2; Dose level 2: RA 80 mg/m2/d and oxaliplatin 130 mg/m2; Dose level 3: RA 110 mg/m2/d and oxaliplatin 130 mg/m2. Results: A total of 15 evaluable patients were enrolled. Median age was 56 (8 male, 7 female). A variety of tumor types were enrolled. A total of 56 cycles were administered. DLT occurred at a dose of RA at 110 mg/m2/d x 5 days and oxaliplatin at 130 mg/m2 and consisted of grade 3 hypophosphatemia and grade 4 atrial fibrillation. At this dose level 2 of 3 enrolled patients also developed grade 3 neutropenia. The MTD and recommended phase II dose was RA at 80 mg/m2/daily x 5 along with oxaliplatin 130 mg/m2 day 5 q 21 days. Three confirmed partial responses were observed in patients with hepatocellular, gallbladder and esophageal cancers. Six patients experienced stable disease. Conclusions: At the MTD combination RA and oxaliplatin is well tolerated and given the response rate and stable diseases observed, phase II studies are recommended. Supported by Grants U01 CA62502, MO1-RR-00080, K23 CA109348–01 from the National Institutes of Health. No significant financial relationships to disclose.

Efficacy and safety of gemcitabine in combination with TH-302 compared with gemcitabine in combination with placebo in previously untreated patients with metastatic or locally advanced unresectable pancreatic adenocarcinoma: The MAESTRO trial.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS4148-TPS4148 ◽  
Author(s):  
Eric Van Cutsem ◽  
Robert J. Fram ◽  
Michael Schlichting ◽  
David P. Ryan
Keyword(s):  
Pancreatic Adenocarcinoma ◽  
Controlled Trial ◽  
Performance Status ◽  
Objective Response ◽  
Locally Advanced ◽  
Predictive Biomarkers ◽  
Treatment Discontinuation ◽  
Phase Iii ◽  
Ecog Performance Status ◽  
Double Blind

TPS4148 Background: Tumors often consist of highly hypoxic subregions that are resistant to chemotherapy and radiotherapy. The investigational hypoxia-targeted drug TH-302 is reduced at its nitroimidazole group, and under hypoxic conditions releases the DNA alkylator bromo-isophosphoramide mustard (Br-IPM). A randomized Phase IIb trial of TH-302 in pts with metastatic or locally advanced unresectable pancreatic adenocarcinoma (PDAC) confirmed a significant PFS improvement (p=0.008) in pts treated with TH-302 at 340 mg/m2+ gemcitabine compared with gemcitabine alone (Borad et al, ESMO 2012). Skin and mucosal toxicities, mainly Grade 1/2, and myelosuppression (thrombocytopenia, neutropenia and anemia) were the most common AEs related to TH-302 and did not lead to increases in treatment discontinuation. Grade 3/4 myelosuppression was more frequent in the TH-302 + gemcitabine arm. AEs leading to treatment discontinuation as well as non-hematological serious AEs were balanced across arms. Methods: This is a Phase III, randomized, double-blind, placebo-controlled trial (NCT01746979) of gemcitabine + TH-302 compared with gemcitabine + placebo in pts with locally advanced unresectable or metastatic PDAC. The study is designed to detect a 25% risk reduction of death with 90% power and two-sided alpha of 5%. A total of 660 pts are planned to be randomized 1:1. Key eligibility criteria include histologically or cytologically confirmed disease, no prior chemotherapy or systemic therapy (except as specified in the protocol), ECOG performance status 0 – 1, and bilirubin ≤ 1.5x upper limit of normal. Randomized pts receive TH-302 + gemcitabine or gemcitabine + placebo in 4-week cycles until progressive disease, intolerable toxicity, or pt withdrawal. The primary objective is to evaluate OS. Secondary objectives include PFS, objective response, and disease control; safety and tolerability; pt-reported QoL and pain; CA 19-9 levels and PK of TH-302; exploratory pharmacogenomic markers and potential predictive biomarkers. Enrollment to the study is ongoing. Clinical trial information: NCT01746979.

Avelumab first-line (1L) maintenance for advanced urothelial carcinoma (UC) in the JAVELIN Bladder 100 trial: Subgroup analysis by duration of treatment-free interval (TFI) from end of chemotherapy to start of maintenance.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4527-4527
Author(s):  
Srikala S. Sridhar ◽  
Thomas Powles ◽  
Yohann Loriot ◽  
Miguel A. Climent Durán ◽  
Shilpa Gupta ◽  
...  
Keyword(s):  
Performance Status ◽  
Objective Response ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Best Supportive Care ◽  
Optimal Timing ◽  
Duration Of Treatment ◽  
Ecog Performance Status ◽  
New Treatment ◽  
Advanced Urothelial Carcinoma

4527 Background: The phase 3 JAVELIN Bladder 100 trial, which enrolled patients (pts) with advanced UC that had not progressed with 1L platinum-containing chemotherapy, showed that maintenance therapy with avelumab + best supportive care (BSC) significantly prolonged overall survival (OS) compared with BSC alone (hazard ratio [HR], 0.69 [95% CI: 0.56, 0.86; 1-sided P= 0.0005]). However, the optimal timing for starting avelumab after completing 1L chemotherapy is unknown. In this post hoc analysis, we report efficacy by duration of the TFI from completion of 1L chemotherapy. Methods: In the JAVELIN Bladder 100 trial (NCT02603432), eligible pts had unresectable locally advanced or metastatic UC without disease progression following 4 to 6 cycles of 1L platinum-containing chemotherapy. Pts were randomized to receive avelumab + BSC (n = 350) or BSC alone (n = 350) after a TFI of 4 to 10 weeks from the last dose of chemotherapy. In this exploratory analysis, subgroups with a TFI of 4 to < 6 weeks ( < 42 days), 6 to < 8 weeks (42 to < 56 days), or 8 to 10 weeks (≥56 days) were evaluated. Results: In the avelumab + BSC and BSC alone arms, the TFI was 4 to < 6 weeks in 143 and 158 pts, 6 to < 8 weeks in 109 and 80 pts, and 8 to 10 weeks in 98 and 110 pts, respectively. Baseline characteristics in these subgroups were generally well balanced between arms. For both arms combined, however, the TFI 4 to < 6 weeks subgroup vs the other 2 subgroups included more pts with visceral metastases (57.8% vs 54.0% and 50.0%), an objective response with 1L chemotherapy (76.4% vs 69.3% and 68.3%), and an ECOG performance status of 1 (44.5% vs 33.3% and 35.6%). OS was prolonged with avelumab + BSC vs BSC alone in all subgroups; the HR was 0.76 (95% CI: 0.546, 1.059) in the TFI 4 to < 6 weeks subgroup (median OS, 19.9 months [95% CI: 16.3, 25.3] vs 13.5 months [95% CI: 11.7, 17.4]), 0.64 (95% CI: 0.404, 1.021) in the TFI 6 to < 8 weeks subgroup (median OS, 26.1 months [95% CI: 19.9, not estimable] vs 21.0 months [95% CI: 10.7, not estimable]), and 0.70 (95% CI: 0.468, 1.035) in the TFI 8 to 10 weeks subgroup (median OS, 20.1 months [95% CI: 13.8, not estimable] vs 14.1 months [95% CI: 11.7, 19.6]). Conclusions: In patients with advanced UC that had not progressed with 1L platinum-containing chemotherapy, avelumab 1L maintenance prolonged OS irrespective of the TFI assessed in this study (4-10 weeks), supporting this new treatment strategy as a standard of care. Differences in duration of TFI were likely related to individual patient- and disease-specific characteristics or logistics and did not impact the OS benefit observed with avelumab 1L maintenance. Clinical trial information: NCT02603432.

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