Clinical Trials Showcase

4:00 pm-5:15 pm

Room: Boisdale

Programme stream(s): Cancer discovery / underpinning research , Treatment

Chair: Richard Wilson, University of Glasgow

This session focuses on the best studies either presented in the last 12 months at other meetings or new data not yet presented, and attract a broad scientific audience interested in either basic, translational or clinical science. Speakers for these sessions are selected from submitted abstracts.

Capivasertib plus fulvestrant versus placebo plus fulvestrant in metastatic ER positive breast cancer (FAKTION): A randomised, double-blind, placebo-controlled, phase II trial
Speaker: Robert Jones
Affiliation: Velindre University NHS Trust, Cardiff, UK

Abstract:

The PI3K/AKT signalling pathway is frequently activated in patients (pts) with estrogen receptor (ER) positive breast cancer (ER+BC) and has been implicated in endocrine therapy resistance. Capivasertib is a highly-selective, oral, small molecule AKT inhibitor. The FAKTION trial investigated addition of capivasertib to fulvestrant for postmenopausal women with ER+ and HER2 negative BC after relapse or disease progression on an aromatase inhibitor (AI).

Method

FAKTION is an investigator-led, double-blind, placebo-controlled, randomised phase II trial. Patients were recruited from 21 UK sites and randomly assigned (1:1) to fulvestrant 500mg with either capivasertib 400mg bd or placebo (4 days on/3 days off starting C1D15). Minimisation according to PIK3CA mutation and PTEN expression status, measurable/non-measurable disease, and primary/secondary endocrine resistance occurred. The primary endpoint was progression-free survival (PFS). The trial had 90% power to detect a hazard ratio of 0.65 at the one-sided 20% significance level. Secondary endpoints included overall survival (OS), objective response and clinical benefit rates, safety and the effect of PI3K/Akt pathway activation on PFS.

Results

140 pts were randomised to fulvestrant + capivasertib (n = 69) or fulvestrant + placebo (n = 71). In the Intention-to-treat analysis, after 112 events, median PFS was 10.3 months (m) for capivasertib compared to 4.8m for placebo (Hazard Ratio (HR) 0.57; 95% CI: 0.39 to 0.84; one-sided p = 0.0017; two-sided 0.0035). Median OS was 26.0m for capivasertib compared to 20.0m for placebo, with a survival difference starting to emerge after 12m (HR = 0.59; 95% CI: 0.34 to 1.05; two-sided p = 0.071). Toxicity data and subgroup analyses including relative capivasertib benefit by PI3K/Akt pathway alteration will be presented.

Conclusion

The trial met its primary endpoint. Addition of capivasertib to fulvestrant for patients with endocrine resistant advanced breast cancer resulted in significantly longer PFS and an improvement in OS. The FAKTION results warrant further investigation.

© 2019 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2019 ASCO Annual Meeting. All rights reserved.

FOxTROT: an international randomised controlled trial in 1052 patients evaluating neoadjuvant chemotherapy for colon cancer
Speaker: Dion Morton, on behalf of the FOxTROT investigators
Affiliation: University of Birmingham, Birmingham, UK

Abstract:

Preoperative chemotherapy is beneficial in many solid cancers but not previously investigated in colon cancer.

Method

Patients with operable, non-obstructed colon cancer, CT-predicted T≥3 Nx M0, were randomised 2:1 to pre&postop (6 weeks chemotherapy; surgery; completion of chemotherapy) or postop (surgery then chemotherapy). KRAS-wt patients could optionally be subrandomised 1:1 to ± panitumumab with preop chemotherapy. In two “dealers’ choices”, clinicians selected the chemotherapy schedule (FOLFOX 72%; CapOx 28%) and total planned chemo duration (24 weeks 94%; 12 weeks 6%). Primary endpoint is freedom from recurrent or persistent disease to 2 yrs, by ITT. Secondary endpoints include safety, histological stage, completeness of resection. A sensitivity analysis assessed the contribution of panitumumab. A single exploratory subgroup analysis was conducted for pMMR/uk (83.6%) vs dMMR (16.4%) cancers.

Results

1052 patients entered in the UK and Scandinavia, median age 65; right:left colon 49:51%.

Pre&post n=698 Postop n=354
went for surgery… 98.2% 97.7%
…of whom: re-operation for postop morbidity 4.3% 7.1% p=0.05
                  R1, R2 or failure to resect 4.8% 11.1% p<0.001
relapse/persistent cancer at 2 yrs 13.6% 17.2% HR=0.75 2p=0.08
T-stage at surgery: ≤2/3/4 (%) 15.8/63.7/20.5 5.8/64.5/29.8 p<0.0001 
N-stage at surgery: 0/1/2 (%) 59.4/25.4/15.2  48.8/25.1/25.9 p<0.0001
Tumour regression grade: 0/1/2-4 (%) 33.9/43.9/19.9 78.8/17.7/0.6 p<0.0001

The sensitivity analysis shows no evidence that panitumumab has contributed to the overall benefits seen in the pre&postop arm. In the subgroup analysis, minimal response to preoperative chemotherapy was seen in MMR tumours, but interaction testing is non-significant.

Conclusion

FOxTROT fell just short of statistical significance for its primary endpoint of 2-year disease control (HR=0.75, 2p=0.08); however, highly significant benefits were seen in terms of reduced postop morbidity, fewer failed or margin-positive resections and marked histological downstaging. This approach may therefore be considered a new treatment option for discussion with patients. Minimal benefit was apparent in dMMR cancers.

© 2019 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2019 ASCO Annual Meeting. All rights reserved.

ABC-06 | A randomised phase III study of Active Symptom Control (ASC) with/without mFOLFOX after progression to Cisplatin-Gemcitabine chemotherapy for patients with advanced biliary tract cancers
Speaker: Angela Lamarca
Affiliation: The Christie NHS Foundation Trust, Manchester, UK

Abstract:

Level A evidence supports use of Cisplatin-Gemcitabine as first-line chemotherapy for advanced biliary tract cancers (ABC); no robust evidence is available for second-line chemotherapy.

Method

Patients diagnosed with ABC with progression to first-line Cisplatin-Gemcitabine were randomised (1:1) to either ASC+mFOLFOX or ASC. Randomisation was stratified by serum albumin levels (<35 vs ≥35 g/L), platinum sensitivity (determined from first-line CisGem) and stage (locally advanced vs metastatic). Primary end-point was overall survival (OS) (multivariable Cox regression adjusted for stratification factors); sample size: 162 patients delivering 148 events were required (80% power; 5% two-sided alpha) for a hypothesised hazard ratio (HR) of 0.63. Assumed median survival for ASC was 4 months. Secondary end-points included progression-free survival (PFS) and response rate (ASC+mFOLFOX arm only).

Results

A total of 162 patients (81 in each arm) were randomised (27-March‘14–04-Jan‘18); median age 65 yrs (range 26-84); sex: 80 (49%) male, 82 (51%) female; primary site: intrahepatic 72 (44%), extrahepatic 45 (28%), gallbladder 34 (21%) and ampullary 11 (7%). Baseline characteristics were balanced between arms except platinum sensitivity (ASC+mFOLFOX 27 patients (33%); ASC 34 patients (42%)). After 150 OS events, the adjusted HR was 0.69 (95%CI 0.50-0.97; p=0.031; ASC+mFOLFOX vs ASC). Median OS (months (m)), 6m and 12m OS-rate (%) were 6.2m, 50.6% and 25.9% for the ASC+mFOLFOX and 5.3m, 35.5%, 11.4% for the ASC arm, respectively. Median PFS was 4.0 months (95%CI 3.2-5.0); response rate 5%, disease control rate 33%. Grade 3/4 toxicities were reported in 48 (59%) and 32 (39%) patients in the ASC+mFOLFOX and ASC arm, respectively; data cleaning is ongoing. Three chemotherapy-related deaths were reported.

Conclusion

Survival with ASC was greater than assumed; ASC+mFOLFOX improved OS after progression to CisGem with a clinically meaningful increase in 6m and 12m OS rate. ASC+mFOLFOX should become standard of care in second-line for ABC.

© 2019 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2019 ASCO Annual Meeting. All rights reserved.

Optimizing Chemotherapy for Frail and Elderly Patients with Advanced Gastroesophageal Cancer (aGOAC): the GO2 Phase III Trial.
Speaker: Peter Hall
Affiliation: University of Edinburgh, Edinburgh, UK

Abstract:

Many patients with aGOAC are elderly and/or frail. We previously compared epirubin/ oxaliplatin/ capecitabine (EOCap) vs OCap vs Cap in a pick-the-winner study and found OCap best. GO2 was designed to find the optimum dose of OCap and to explore the use of baseline geriatric assessment to individualize doses for Overall Treatment Utility (OTU), a composite of clinical benefit, tolerability, QoL and patient value.

Method

Patients with aGOAC were eligible if unsuitable for full-dose EOCap due to age or frailty, but fit for OCap. Baseline assessment included QoL; symptoms; functioning; comorbidity; frailty. Randomization was 1:1:1 to dose Level A (Ox 130 mg/m2d1, Cap 625 mg/m2bd d1-21, q21d), B (80% A doses) or C (60% A doses). At 9 weeks, patients were scored for OTU. Non-inferiority (vs A) was assessed using PFS with boundary HR 1.34 based on discussion with patients and clinicians.

Results

512 pts were randomised, 2014-17, 61 UK centres.


Level A

Level B

Level C

Pts (PFS events)

170 (142)

171 (147)

173 (149)

Median age

76

76

77

% PS ≥2

31

32

31

% Severely Frail

61

56

58

% any Gr ≥3 non-haem AE

56

56

49

Median PFS mo

4.9

4.1

4.3

OTU wk 9: % Good/mod./poor

35/34/31

36/26/38

43/27/29

Median OS mo

7.5

6.7

7.6

Non-inferiority of PFS is confirmed for Level B vs A (HR 1.09, CI 0.89-1.32) and for Level C vs A (HR 1.10, CI 0.90-1.33). Level C pts had least toxicity and best OTU. OTU was optimal with Level C even in non-frail and PS0-1 pts; no group benefited more from the higher dose levels.

Conclusion

This is the largest RCT to date investigating frail elderly aGOAC pts, and should guide future treatment. The lowest dose was non-inferior for PFS and achieved better overall treatment utility.

© 2019 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2019 ASCO Annual Meeting. All rights reserved.

ACUFOCIN: Randomised clinical trial of ACUpuncture plus standard care versus standard care alone FOr Chemotherapy Induced peripheral Neuropathy (CIPN)
Speaker: Jacqui Stringer
Affiliation: The Christie NHS Trust

Abstract:

CIPN is a dose limiting toxicity, which poses a major clinical challenge. Literature would suggest that acupuncture offers promise in managing neuropathy. This study aims to explore the use of acupuncture with standard care (Acu +SC) against SC alone, to reduce symptoms of CIPN.

Method

A phase II, randomised, parallel group design was used to investigate the effectiveness of a 10 week course of acupuncture to manage CIPN. Patients experiencing CIPN ≥ Grade II (CTCAE v4.03), recording a ‘Most Troublesome’ CIPN symptom score of ≥ 3 using the “Measure Yourself Medical Outcome Profile” (MYMOP 2), were randomised (1:1) to either Acu+SC or SC alone. The primary end-point was a ≥ 2 point improvement (success) in MYMOP2 score at week 10  (logistic regression adjusted for stratification factors and baseline MYMOP2 score). The necessary sample size was 100 patients;120 were randomised to allow for attrition (90% power; 10% one-sided alpha), for a hypothesised improvement in success proportions from 30% to 55%. 

Results

120 patients were randomised to ACUFOCIN; diagnosis: breast 61 (51%), multiple myeloma 9 (8%), GI 48 (40%), gynaecological 2 (2%). MYMOP2 score for most troubling CIPN symptom at baseline: 3-4 33 (28%), 5-6 87 (73%).  CTCAE CIPN  at baseline; grade II 103 (86%), grade III 17 (14%). Baseline characteristics were balanced between arms. Primary outcome data were available for 108 participants with 36/54 (67%) successes in the Acu+SC arm compared to 18/55 (33%) in the SC arm. Adjusted success odds ratio was 4.3 (95% CI 1.9-9.6; p < 0.001; Acu+SC vs SC). Additionally, 27/53 (51%) participants achieved a CIPN success (grade ≤ I) in the Acu+SC arm compared to 4/56 (7%) in the SC arm with adjusted odds ratio 13.1 (95% CI 4.1-41.7; p < 0.001; Acu+SC vs SC).

Conclusion

In this patient cohort, a 10 week course of acupuncture significantly improved symptoms of CIPN. These results support further investigation within a phase III trial.

BEACON: A Randomised, Phase 3 Study of Encorafenib and Cetuximab +/- Binimetinib vs. Choice of Either Irinotecan or FOLFIRI plus Cetuximab in BRAF V600E–Mutant Metastatic Colorectal Cancer Patients
Speaker: Harpreet Wasan
Affiliation: Hammersmith Hospital, London, UK

Abstract:

BRAF mutations are identified in up to 15% of metastatic CRC (mCRC) pts and confer poor prognosis. In pts who are refractory to initial therapy, objective response rates (ORR) to standard chemotherapy and biologic combinations are generally <10%, with median progression-free survival (PFS) and overall survival (OS) approximately 2 and 4–6 months (mo), respectively. A 30 pt safety lead-in (SLI) of the BEACON study assessed the safety, tolerability, and efficacy of the combination of encorafenib (ENCO) + binimetinib (BINI) + cetuximab (CETUX) in pts with BRAF V600E–mutant mCRC after failure of 1 or 2 prior regimens, demonstrated a confirmed ORR of 48% [95% CI: 29.4, 67.5], including complete responses (CR) in 3 pts, median PFS of 8.0 mo [95% CI: 5.9, 9.3], and mature median OS of 15.3 mo [95% CI: 9.6, NR]. The combination was generally well tolerated, confirming the dose selection of the triplet combination for the randomized portion of the study.

Method

The BEACON Study (NCT02928224) is a multicenter, randomized, open-label, 3-arm, phase 3 study to evaluate ENCO+CETUX with/without BINI (vs. investigator’s choice of irinotecan or FOLFIRI + CETUX (control) in pts with BRAF V600E‒mutant mCRC whose disease has progressed after 1 or 2 prior regimens in the metastatic setting. 665 pts were randomized. The primary endpoints are OS and ORR (blinded central review) comparing the triplet to the control arm; secondary endpoints include PFS, duration of response, time to response, and comparisons of the doublet to the triplet and control arms.

Results

Results of the initial analysis, including efficacy and safety, will be reported.

Conclusion

In the SLI, the combination of ENCO+BINI+CETUX showed encouraging activity in pts with BRAF V600E‒mutant mCRC. This regimen may be a new standard of care if these results are confirmed in the randomized portion of the study.