The rising number of prematurely halted oncology RCTs, often with small sample sizes, raises ethical concerns about overestimating treatment benefits and calls for more transparent guidelines from Data Safety Monitoring Committees.
Is it better for industry or for patients to end an early oncology trial? (8)
author: Andreas Tjandra, drg | publisher: drg. Andreas Tjandra, Sp. Perio, FISID
Treatment
Disease
Trial starting date versus end of the enrolment versus date of publication
DSMC
Primary end point versus end point used in interim analysis
Planned versus interim sample size
Rationale for planning interim analysis
Interim analysis consequences
Control group
Melphalan + prednisone + thalidomidea
Multiple Myeloma
May 2000 versus August 2005 versus October 2007
Y
OS versus OS
500 versus 447 patients
No. of enrolled patients
Stop enrolment
A
Temsirolimusa
Advanced renal cell carcinoma
July 2003 versus April 2005 versus May 2007
Y
OS versus OS
600 versus 446 events
No. of events
Disclosure of results
A
Sunitiniba
Metastatic renal cell carcinoma
August 2004 versus October 2005 versus January 2007
Y
PFS versus PFS
471 events versus NA
Cut-off date
Crossover to treatment group
A
Sorafeniba
Advanced clear-cell renal cell carcinoma
November 2003 versus March 2005 versus January 2007
Y
OS versus PFS
540 versus 363 events
No. of events
Crossover to treatment group + stop enrolment
P
Paclitaxel + carboplatin + bevacizumaba
Non-small-cell lung cancer
July 2001 versus April 2004 versus December 2006
Y
OS versus OS
650 versus 455 events
No. of events
Disclosure of results
A
Lapatinib + capecitabinea
HER-2-positive metastatic breast cancer
March 2004 versus NA versus December 2006
Y
TtP versus TtP
266 versus 114 events
No. of events
Crossover to treatment group + stop enrolment
A
Sunitiniba
Advanced gastrointestinal stromal tumour
December 2003 versus January 2005 versus October 2006
Y
TtP versus TtP
281 versus 149 events
No. of events
Crossover to treatment group
P
FU + leucovorina + oxaliplatino (FOLFOX4)a
Metastatic colorectal cancer
April 2001 versus April 2002 versus July 2006
Y
TtP versus TtP
550 versus 305 patients
No. of events
Stop enrolment
A
Uracil + tegafur
Stage III rectal cancer
October 1996 versus April 2001 versus April 2006
Y
RFS versus RFS and OS
400 versus 274 patients
Cut-off date
Disclosure of results
NT
Carboplatin
Epithelial ovarian cancer
November 1994 versus July 1998 versus January 2006
Y
TtP versus TtP
190 versus 120 events
No. of events
Stop enrolment
A
Methotrexate, vinblastine, doxorubicin/epirubicin, cisplatin
Advanced bladder cancer
May 1987 versus December 1990 versus January 2006
N
PFS versus PFS
NA
NA
Stop enrolment
NT
Trastuzumab + adjuvant chemotherapya
HER-2 positive breast cancer
May 2003 versus November 2004 versus October 2005
Y
DFS versus DFS
710 versus 394 events
No. of events
Stop enrolment + disclosure of results
A
Trastuzumab (1-year arm + 2-year arm)a
HER-2-positive early-stage invasive breast cancer
December 2001 versus March 2005 versus October 2005
Y
DFS versus DFS
951 versus 347 events
No. of events
Disclosure of results
NT
Bevacizumab + (irinotecan, FU, leucovorin) and bevacizumab + (FU, leucovorin)a
Metastatic colorectal cancer
NA versus NA versus May 2005
Y
OS versus OS
After 313 patients enrolled
No. of enrolled patients
Stop enrolment
A+ P
Letrozolea
Adjuvant therapy in receptor-positive breast cancer
August 1998 versus September 2002 versus November 2003
Y
DFS versus DFS
515 versus 171 events
No. of events
Disclosure of results
P
Gemcitabine
Advanced or metastatic adenocarcinoma of the pancreas
December 1997 versus July 1999 versus September 2003
Y
OS versus OS and PFS
350 patients versus 140 events
No. of events
Stop enrolment + crossover to treatment group
A
Bevacizumab
Metastatic renal cell carcinoma
Oct 1998 versus Sep 2001 versus Jul 2003
Y
TtP, RR versus TtP
120 versus 110 patients
Cut-off date
Crossover to treatment group
P
Idoxifene
Postmenopausal metastatic breast cancer
December 1996 versus May 1999 versus February 2003
N
RR, TtP versus RR, TtP
440 versus 321 patients
No. of enrolled patients
Trial stopped for economic consideration
A
ChlVPP/EVA hybrid
Hodgkin's disease
September 1992 versus September 1996 versus July 2002
N
NA
80 versus 60 events
No. of events
Stop enrolment
A
Irinotecan + cisplatin
Metastatic small-cell lung cancer
November 1995 versus November 1998 versus January 2002
Y
OS versus OS
230 versus 230 patients
No. of enrolled patients
Stop enrolment
A
Vinblastine + doxorubicin + irradiation
Hodgkin's disease
NA versus April 2000 versus November 2001
Y
FFS versus FFS
420 versus 348 patients
No. of enrolled patients
Stop enrolment
A
Gemcitabine + vinorelbine
Advanced non-small-cell lung cancer
June 1997 versus May 1999 versus July 2000
Y
OS versus OS
240 versus 120 patients
No. of enrolled patients
Stop enrolment
A
Gemcitabine + vinorelbine + cisplatin
Advanced non-small-cell lung cancer
April 1997 versus April 1999 versus April 2000
N
OS versus OS
240 versus 120 patients
No. of enrolled patients
Stop enrolment
A
Lipiodol iodine-131
Adjuvant in resectable hepatocellular carcinoma
April 1992 versus August 1997 versus March 1999
N
Recurrence rate, recurrence sites, DFS, OS versus DFS
120 versus 43 patients
No. of enrolled patients
Stop enrolment
NT
Doxorubicin or ethoglucid
Adjuvant in superficial transitional cell bladder carcinoma
December 1979 versus December 1983 versus August 1997
N
NA
NA versus 206 patients
No. of enrolled patients
Stop enrolment
NT
Table 1
Summarised data on oncological trials (N=25) stopped early for benefit
Serial posts:
-
Magnetic Field Affecting Bone Healing (3)
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Is it better for industry or for patients to end an early oncology trial? (8)
| Treatment | Disease | Trial starting date versus end of the enrolment versus date of publication | DSMC | Primary end point versus end point used in interim analysis | Planned versus interim sample size | Rationale for planning interim analysis | Interim analysis consequences | Control group |
|---|---|---|---|---|---|---|---|---|
| Melphalan + prednisone + thalidomidea | Multiple Myeloma | May 2000 versus August 2005 versus October 2007 | Y | OS versus OS | 500 versus 447 patients | No. of enrolled patients | Stop enrolment | A |
| Temsirolimusa | Advanced renal cell carcinoma | July 2003 versus April 2005 versus May 2007 | Y | OS versus OS | 600 versus 446 events | No. of events | Disclosure of results | A |
| Sunitiniba | Metastatic renal cell carcinoma | August 2004 versus October 2005 versus January 2007 | Y | PFS versus PFS | 471 events versus NA | Cut-off date | Crossover to treatment group | A |
| Sorafeniba | Advanced clear-cell renal cell carcinoma | November 2003 versus March 2005 versus January 2007 | Y | OS versus PFS | 540 versus 363 events | No. of events | Crossover to treatment group + stop enrolment | P |
| Paclitaxel + carboplatin + bevacizumaba | Non-small-cell lung cancer | July 2001 versus April 2004 versus December 2006 | Y | OS versus OS | 650 versus 455 events | No. of events | Disclosure of results | A |
| Lapatinib + capecitabinea | HER-2-positive metastatic breast cancer | March 2004 versus NA versus December 2006 | Y | TtP versus TtP | 266 versus 114 events | No. of events | Crossover to treatment group + stop enrolment | A |
| Sunitiniba | Advanced gastrointestinal stromal tumour | December 2003 versus January 2005 versus October 2006 | Y | TtP versus TtP | 281 versus 149 events | No. of events | Crossover to treatment group | P |
| FU + leucovorina + oxaliplatino (FOLFOX4)a | Metastatic colorectal cancer | April 2001 versus April 2002 versus July 2006 | Y | TtP versus TtP | 550 versus 305 patients | No. of events | Stop enrolment | A |
| Uracil + tegafur | Stage III rectal cancer | October 1996 versus April 2001 versus April 2006 | Y | RFS versus RFS and OS | 400 versus 274 patients | Cut-off date | Disclosure of results | NT |
| Carboplatin | Epithelial ovarian cancer | November 1994 versus July 1998 versus January 2006 | Y | TtP versus TtP | 190 versus 120 events | No. of events | Stop enrolment | A |
| Methotrexate, vinblastine, doxorubicin/epirubicin, cisplatin | Advanced bladder cancer | May 1987 versus December 1990 versus January 2006 | N | PFS versus PFS | NA | NA | Stop enrolment | NT |
| Trastuzumab + adjuvant chemotherapya | HER-2 positive breast cancer | May 2003 versus November 2004 versus October 2005 | Y | DFS versus DFS | 710 versus 394 events | No. of events | Stop enrolment + disclosure of results | A |
| Trastuzumab (1-year arm + 2-year arm)a | HER-2-positive early-stage invasive breast cancer | December 2001 versus March 2005 versus October 2005 | Y | DFS versus DFS | 951 versus 347 events | No. of events | Disclosure of results | NT |
| Bevacizumab + (irinotecan, FU, leucovorin) and bevacizumab + (FU, leucovorin)a | Metastatic colorectal cancer | NA versus NA versus May 2005 | Y | OS versus OS | After 313 patients enrolled | No. of enrolled patients | Stop enrolment | A+ P |
| Letrozolea | Adjuvant therapy in receptor-positive breast cancer | August 1998 versus September 2002 versus November 2003 | Y | DFS versus DFS | 515 versus 171 events | No. of events | Disclosure of results | P |
| Gemcitabine | Advanced or metastatic adenocarcinoma of the pancreas | December 1997 versus July 1999 versus September 2003 | Y | OS versus OS and PFS | 350 patients versus 140 events | No. of events | Stop enrolment + crossover to treatment group | A |
| Bevacizumab | Metastatic renal cell carcinoma | Oct 1998 versus Sep 2001 versus Jul 2003 | Y | TtP, RR versus TtP | 120 versus 110 patients | Cut-off date | Crossover to treatment group | P |
| Idoxifene | Postmenopausal metastatic breast cancer | December 1996 versus May 1999 versus February 2003 | N | RR, TtP versus RR, TtP | 440 versus 321 patients | No. of enrolled patients | Trial stopped for economic consideration | A |
| ChlVPP/EVA hybrid | Hodgkin's disease | September 1992 versus September 1996 versus July 2002 | N | NA | 80 versus 60 events | No. of events | Stop enrolment | A |
| Irinotecan + cisplatin | Metastatic small-cell lung cancer | November 1995 versus November 1998 versus January 2002 | Y | OS versus OS | 230 versus 230 patients | No. of enrolled patients | Stop enrolment | A |
| Vinblastine + doxorubicin + irradiation | Hodgkin's disease | NA versus April 2000 versus November 2001 | Y | FFS versus FFS | 420 versus 348 patients | No. of enrolled patients | Stop enrolment | A |
| Gemcitabine + vinorelbine | Advanced non-small-cell lung cancer | June 1997 versus May 1999 versus July 2000 | Y | OS versus OS | 240 versus 120 patients | No. of enrolled patients | Stop enrolment | A |
| Gemcitabine + vinorelbine + cisplatin | Advanced non-small-cell lung cancer | April 1997 versus April 1999 versus April 2000 | N | OS versus OS | 240 versus 120 patients | No. of enrolled patients | Stop enrolment | A |
| Lipiodol iodine-131 | Adjuvant in resectable hepatocellular carcinoma | April 1992 versus August 1997 versus March 1999 | N | Recurrence rate, recurrence sites, DFS, OS versus DFS | 120 versus 43 patients | No. of enrolled patients | Stop enrolment | NT |
| Doxorubicin or ethoglucid | Adjuvant in superficial transitional cell bladder carcinoma | December 1979 versus December 1983 versus August 1997 | N | NA | NA versus 206 patients | No. of enrolled patients | Stop enrolment | NT |
Table 1
Summarised data on oncological trials (N=25) stopped early for benefit
- Magnetic Field Affecting Bone Healing (3)
- Is it better for industry or for patients to end an early oncology trial? (8)