WELCOME TO THE INTERACTIVE PROGRAM OF THE IGCS 2023 MEETING
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Session Introduction
SEMINAL: An international randomized phase III trial comparing radical hysterectomy vs simple hysterectomy in patients with low-risk early-stage cervical cancer
Abstract
Abstract Body
Background:
In the last 2 decades, there has been a trend towards less radical surgery in patients with low-risk cervical cancer. Retrospective data suggested that less radical surgery may be safe and associated with less morbidity. The objective of this non-inferiority phase III prospective randomized trial was to compare RH to SH in women with low-risk early-stage cervical cancer (LRESCC).
Methods:
Women with LRESCC defined as FIGO 2018 1A2 or 1B1 disease were randomized to receive RH or SH after stratification by cooperative group, intended use of sentinel node mapping, stage, histological type, and tumour grade. The primary endpoint was pelvic recurrence rate at 3 years (PRR3). Non-inferiority of SH to RH is claimed when the 95% upper one-sided confidence limit (95% UCL) for the difference in PRR3 of SH to RH (DPRR3), calculated by the Kaplan-Meier method, is lower than or equal to 4%. Primary intention to treat (ITT) analysis included all patients randomized. Per-protocol (PP) analysis included eligible patients at baseline and without evidence of more advanced disease found at the time of surgery or final pathology, based on treatment actually received. Secondary endpoints included extrapelvic relapse-free survival (ERFS), overall survival (OS), and relapse free survival.
Results:
700 women were enrolled from December 2012 to November 2019. Patient characteristics were well balanced: median age was 44 (24-80); 91.7% had FIGO stage 1B1 disease and 61.7% had squamous histology. 50% of the hysterectomies were done laparoscopically (56% SH vs. 44% RH), 25% robotically (24% vs. 25%) and 23% abdominally (17% vs. 29%). On final pathology, lymph node metastasis occurred in 3.7% (3.3% SH and 4.4% RH), positive margins in 2.5% (2.1% SH and 2.9% RH), and lesions >2cm in 4.2% (4.4% SH and 4.1% RH). A total of 8.8% of women received post-surgical adjuvant therapy (9.2% in SH and 8.4% in RH). With a median follow-up of 4.5 years, 21 pelvic recurrences were identified (11 in SH and 10 in RH group). The PRR3 was 2.52% with SH and 2.17% with RH (DPRR3 0.35% with 95% UCL 2.32%) in ITT analysis; 2.8% with SH and 2.3% with RH (DPRR3 0.42% with 95% UCL 2.56%) in PP analysis. The 3-year ERFS and OS were respectively 98.1% and 99.1% with SH; 99.7% and 99.4% with RH. RH had significantly higher surgery related incidence of urinary incontinence (11.0% vs. 4.7% with SH; p=0.003) and urinary retention (9.9% vs. 0.6% with SH; p<0.0001) during follow-up.
Conclusion:
The pelvic recurrence rate at 3 years in women with low risk early-stage cervical cancer who underwent a simple hysterectomy was not inferior to a radical hysterectomy and was associated with fewer surgical adverse events.
IS MINIMALLY INVASIVE SURGERY SAFE FOR CERVICAL CANCER PATIENTS WITH A DIAMETER OF LESS THAN 2 CM? (MISAFE): GYNECOLOGIC ONCOLOGY RESEARCH INVESTIGATORS COLLBORATION STUDY (GORILLA-1003)
Abstract
Introduction
To identify clinicopathologic factors associated with disease recurrence for patients with 2018 FIGO stage IA with lymphovascular invasion (LVSI) to IB1 cervical cancer treated with minimally invasive surgery (MIS).
Methods
A total of 722 early-stage cervical cancer patients between January 2010 and February 2021 were identified. All possible clinicopathologic factors related to disease recurrence were analyzed. Disease-free survival (DFS) and overall survival (OS) rates were estimated using the Kaplan-Meier method. To determine prognostic factors for DFS, a Cox proportional hazard regression model was used.
Results
Of 722 patients, 49 (6.8%) showed disease recurrence (37 pelvis, 1 para-aortic lymph node, and 11 peritoneum). Five-year DFS and OS rates were 90.7% and 98.1%, respectively. In multivariate analysis, risk factors associated with disease recurrence were residual disease in the remaining cervix (OR, 4.693; 95% CI, 3.719 – 5.667; p = 0.002), intracorporeal colpotomy (OR, 2.960; 95% CI, 1.703 – 3.161; p = 0.017), and positive resection margin (OR, 3.415; 95% CI, 2.351 – 4.479; p = 0.024). The non-conization group had a higher percentage of stage IB1 (77.4% vs. 64.6%; p = 0.004) and larger tumor (16 mm vs. 10 mm; p < 0.001) than the conization group. Intracorporeal colpotomy and residual disease in the remaining cervix were independent variables associated with disease recurrence in patients undergoing MIS following conization.
Conclusion/Implications
During MIS, early-stage cervical cancer patients with tumors less than 2 cm can be vulnerable to peritoneal recurrences. Preoperative conization itself may not lower the disease recurrence in early-stage cervical cancer patients undergoing MIS.
Discussion and Q&A
EFFICACY AND SAFETY RESULTS FROM SKYSCRAPER-04: AN OPEN-LABEL RANDOMIZED PHASE 2 TRIAL OF TIRAGOLUMAB PLUS ATEZOLIZUMAB FOR PD-L1-POSITIVE RECURRENT CERVICAL CANCER
Abstract
Introduction
Immune checkpoint inhibitors are active in advanced cervical cancer. SKYSCRAPER-04 (NCT04300647) evaluated dual blockade with tiragolumab (anti-TIGIT) and atezolizumab (anti-PD-L1) (tira+atezo), an approach hypothesized to overcome immune suppression and restore immune response.
Methods
Eligible patients had measurable (per investigator assessment) PD-L1-positive recurrent/persistent cervical cancer after 1-2 prior chemotherapy lines (including ≥1 platinum-based regimen). Patients were randomized 3:1 to atezolizumab 1200mg with or without tiragolumab 600mg q3w until unacceptable toxicity/progression. Crossover to tira+atezo was permitted after unequivocal progression during single-agent atezolizumab. Stratification factors were ECOG PS, prior (chemo)radiotherapy, and disease status. The primary endpoint was independent review committee (IRC)-assessed confirmed objective response rate (ORR) per RECIST v1.1 in all treated patients randomized to tira+atezo. An ORR ≥21% (1-sample z-test p≤0.0245) was required to demonstrate statistically significant improvement versus a 14.6% historical reference [Chung, 2019]. Secondary endpoints included IRC-assessed progression-free survival, overall survival, and pre-crossover safety.
Results
Prior therapy in 171 treated patients included bevacizumab in 35%, (chemo)radiotherapy in 80%, and paclitaxel in 93%. IRC-assessed ORRs were 19.0% with tira+atezo and 15.6% with atezo alone (Table). In post hoc exploratory analyses of patients with measurable disease per IRC assessment, ORRs were 21.6% (tira+atezo) and 15.8% (atezo). There were no new safety signals. In a post hoc follow-up analysis, 15% of patients remained on treatment and 15/45 initially randomized to atezo had crossed over to tira+atezo.
Conclusion/Implications
The ORR with tira+atezo was numerically but not significantly higher than the historical benchmark. This is the first reported phase 2 cervical cancer trial targeting TIGIT and PD-L1 concurrently.
IGNITE: A PHASE II SIGNAL-SEEKING TRIAL OF ADAVOSERTIB TARGETING RECURRENT HIGH GRADE SEROUS OVARIAN CANCER WITH CYCLIN E1 OVER-EXPRESSION WITH AND WITHOUT GENE AMPLIFICATION
Abstract
Introduction
Cyclin E1 amplification and over-expression is associated with platinum resistance in high grade serous ovarian cancer (HGSC), and may predict response to WEE1 inhibition. Adavosertib, a WEE1 inhibitor, has activity in unselected women with recurrent ovarian and endometrial cancer. We aimed to evaluate the efficacy of adavosertib in women with recurrent platinum resistant HGSC (PR-HGSC) with cyclin E1 over-expression, with and without gene amplification.
Methods
IGNITE is a multicentre, Phase 2 trial with 2 cohorts of PR-HGSC patients. Cohort 1 were cyclin E1 amplified (≥8 copies by FISH) and over-expressed (H-score>50), and Cohort 2 were non-amplified. Adavosertib 300mg PO was given daily on days 1-5 and 8-12 q21-day cycle (dose was reduced to 200mg after n=71 due to safety concerns). The primary endpoint was clinical benefit (CB) defined as no progression for ≥ 18 weeks. Here we present the 18-week CB rate (CBR) and overall response rate (ORR), with data cut-off of Apr-2023.
Results
From Jan-2020 to Oct-2022, 80 patients (Cohort 1 n=21; Cohort 2 n=59) were accrued. Median age was 64 years (range 42-84), 83% had ≥2 prior chemotherapy lines. For Cohort 1, ORR=38% and CBR=53%. For Cohort 2, ORR=45% and CBR=48%. Treatment related adverse events occurred in 78 patients (97%). Dose reduction was required in 36 (45%) patients, mostly for neutropenia or diarrhoea. Four patients (5%) died from treatment (sepsis n=3; thrombocytopenia n=1).
Conclusion/Implications
Adavosertib demonstrated activity in biomarker selected patients with PR-HGSC. Study accrual was halted early due to concern regarding rates of myelotoxicity.
Discussion and Q&A
LBA: EFFICACY AND SAFETY OF AVUTOMETINIB + DEFACTINIB IN RECURRENT LOW-GRADE SEROUS OVARIAN CANCER FOLLOWING PRIOR SYSTEMIC THERAPY
Abstract
Introduction
Avutometinib is a novel small molecule RAF/MEK clamp. FAK activation is a resistance mechanism to RAF/MEK inhibition; defactinib, a small molecule FAK inhibitor, has shown synergistic antitumor activity with avutometinib. Avutometinib + defactinib demonstrated a 45% ORR and a mild to moderate, manageable/reversible safety profile in heavily pretreated (mLoT=4) recurrent LGSOC (KRAS mt + wt) (ENGOT-ov60/GOG-3052/RAMP 201, NCT04625270).
Methods
This post-hoc analysis of the phase 2 ENGOT-ov60/GOG-3052/RAMP 201 study in recurrent LGSOC (06Apr2023 data cutoff) was performed to assess efficacy (Part A; confirmed ORR via blinded independent central review) and safety (all treated patients) in the context of 1) lines of prior systemic therapy (1-3 LoT, ≥4 LoT) and 2) best response to most recent prior treatment in the metastatic/recurrent setting (PR/CR, no PR/CR; as assessed by treating investigator).
Results
In the combination arm, similar ORRs were observed in patients that were treated with 1-3 (5/11, 45.5%) and ≥4 LoT (8/18, 44.4%) (Table 1). Prior to enrollment in RAMP 201, only 2/23 (8.7%) patients responded to their last prior treatment, whereas the combination of avutometinib + defactinib yielded an ORR of 43.5% (10/23) in this subgroup (Table 2). The safety profiles of avutometinib + defactinib were similar in the less and more heavily pretreated subgroups, and both analyses were consistent with previously reported safety data. The majority of TRAEs were mild to moderate, manageable/reversible.
Conclusion/Implications
Avutometinib + defactinib demonstrated robust efficacy (ORR) in recurrent LGSOC irrespective of the number of prior therapies, and for most of which, response to previous therapy was poor.
LBA: A RANDOMIZED, PHASE II/III STUDY OF PEGYLATED-LIPOSOMAL-DOXORUBICIN AND ATEZOLIZUMAB (IND #134427) VERSUS PEGYLATED-LIPOSOMAL-DOXORUBICIN, BEVACIZUMAB AND ATEZOLIZUMAB VERSUS PEGYLATED-LIPOSOMAL-DOXORUBICIN AND BEVACIZUMAB IN PLATINUM-RESISTANT OVARIAN CANCER (NRG-GY009)
Abstract
Introduction
In this multicentre randomized, phase II/III trial, we sought to examine if the 1) combination of anti-programmed death ligand 1 (PD-L1) monoclonal antibody atezolizumab (ATEZO) with pegylated-liposomal- doxorubicin (PLD) [Arm 1] and/or 2) addition of ATEZO to PLD and bevacizumab (BEV) [Arm 2] result in an improvement in survival for patients with platinum resistant ovarian cancer (PROC) compared to the standard PLD/BEV [Arm 3].Methods
Patients were randomly assigned 1:1:1 to PLD/ATEZO, PLD/BEV/ATEZO or PLD/BEV (IV PLD 40mg/m2 q4weeks; BEV 10mg/kg q2weeks; ATEZO 800mg q2weeks). Key eligibility: 1-2 prior lines of therapy (no PLD), ECOG 0-2, and RECIST measurable/evaluable PROC. No stratification by PD-L1 status. The phase II primary endpoint was PFS. The phase III coprimary endpoints were PFS/OS.Results
From 05/2017-10/2021 444 patients with PROC were enrolled. The median age was 63yrs (35-86). All had received prior chemotherapy; 434 (97.7%) prior surgery and 9 (2%) prior biological therapy. At the phase III interim analysis Arm 1 (PLD/ATEZO) was discontinued for futility. The phase III OS/PFS analysis included accruals to Arms 2 (PLD/BEV/ATEZO) and 3 (PLD/BEV) from all phases. With median follow-up of 47 months, median PFS was 7.4 months and 5.6 months (HR 0.79 with 99.99% 1-sided CI 0.0-1.21), and median OS was 14.9 months and 12.3 months (HR 0.80; 98.78% 1-sided CI 0.00-1.06; 1-sided p=0.038) for Arms 2 and 3, respectively. Adverse events were as expected.Conclusion/Implications
The addition of ATEZO to PLD/BEV did not result in a statistically significant longer OS than PLD/BEV in PROC. Subset analysis are planned to evaluate survival outcomes with high PD-L1 expression (NRG-GY009/NCT02839707).
Discussion and Q&A
SEMINAL: A randomised phase III trial of induction chemotherapy followed by chemoradiation compared with chemoradiation alone in locally advanced cervical cancer. The GCIG INTERLACE trial
Abstract
Abstract Body
Background
Locally advanced cervical cancer (LACC) is treated with chemoradiation (CRT). However, many patients relapse and die from metastatic disease. A feasibility study demonstrated a good response rate to the short course weekly induction chemotherapy (IC) delivered before standard CRT and the INTERLACE trial investigated whether this approach improves both progression free survival (PFS) and overall survival (OS).
Methods
Women with squamous, adeno or adenosquamous carcinoma FIGO (2008) stage IB1 node positive, IB2, II, IIIB, IVA were eligible. Patients were randomised (1:1) to receive either CRT alone (5 cycles weekly cisplatin) or IC (6 weeks carboplatin AUC2 and paclitaxel 80mg/m2) followed by the same CRT in week 7. Mandated minimum total EQD2 dose 78Gy to Point A with 3D brachytherapy recommended. All centres underwent radiation quality assurance. Primary endpoints were PFS (target hazard ratio [HR] 0.65) and OS (target HR 0.65-0.70).
Results
500 Patients were recruited from 32 centres in 5 countries (Nov 2012 – Nov 2022). Median age 46 (range 24-78 years). Stage distribution was: IB1/2;9%, II;77%, IIB;11% and IVA;3%. 57% were node negative and 82% squamous subtype. Arms were balanced.
92% of IC patients had 5/6 cycles of carboplatin/paclitaxel. Median interval from IC to CRT was 7 days. 84% IC/CRT vs. 89% (CRT alone) had 4/5 cycles cisplatin. In the CRT arm 92% and 89% completed external beam and brachytherapy respectively; corresponding figures in the IC/CRT arm were 97% and 95%. The median overall treatment time for CRT was 45 days in both arms.
Grade ≥3 adverse events were seen in 59% (IC/CRT) vs. 48% (CRT alone).
Median follow up 64 months. 5-year PFS rate is 73% with IC/CRT and 64% with CRT alone (HR 0.65; 95%CI:0.46-0.91, p=0.013). The corresponding 5 year OS rates are 80% and 72% (HR 0.61:95%CI:0.40-0.91, p=0.04).
Conclusions
Induction chemotherapy followed by CRT significantly improves PFS and OS in LACC and should be considered a new standard of care. INTERLACE recruited patients from diverse health care settings demonstrating that IC followed by CRT is feasible in all countries.
Clinical trial identification
EUDRACT no: 2011-001300-35
SEMINAL: Phase 3 MIRASOL (GOG 3045/ENGOT-ov55) Trial: Mirvetuximab Soravtansine (MIRV) Prolongs Overall Survival vs Investigator’s Choice Chemotherapy (IC) in Platinum-Resistant Ovarian Cancer (PROC) with High Folate Receptor-Alpha (FRα) Expression
Abstract
Abstract Body
Introduction: Mirvetuximab soravtansine (MIRV), an antibody drug conjugate targeting FRα, demonstrated clinically meaningful antitumor activity in a single arm trial reported previously (Matulonis, JCO 2023). MIRASOL is a randomized phase 3 trial to confirm the efficacy of MIRV vs IC chemotherapy in patients (pts) with FRα high, PROC.Methods: 453 pts with FRα high (Roche FOLR1 Assay) PROC were randomized 1:1 to MIRV 6 mg/kg, adjusted ideal body weight, Day 1 of a 21-day cycle or IC: paclitaxel, pegylated liposomal doxorubicin, or topotecan. The primary efficacy endpoint was progression-free survival (PFS) by investigator (INV) with key secondary endpoints ORR, and overall survival (OS), in hierarchical order; other endpoints included safety and tolerability.
Results: With a data cutoff of March 6, 2023, 227 pts were randomized to the MIRV arm; 226 to the IC arm. Median follow-up was 13.1 months. Baseline characteristics were well balanced across arms; 14% of pts had one, 39% two, and 47% three prior lines of therapy (LOT); 62% received prior bev; and 55% received prior PARPi therapy. The study met its primary and key secondary endpoints with statistically significant results in PFS (INV), ORR (INV), and OS (Table). In subset analyses, pts with 1 or 2 PLOT, PFS HR was 0.61 (0.45, 0.81) and ORR 46% vs 15%; and 3 PLOT, PFS HR was 0.71 (0.52, 0.98) and ORR 38% vs 18%, favoring MIRV. In pts with prior PARPi, PFS HR was 0.58 (0.43, 0.78) and ORR 45% vs 17%. In PARPi naïve, PFS HR was 0.74 (0.54, 1.03) and ORR 40% vs 14%, favoring MIRV.
The adverse event (AE) profile of MIRV was consistent with prior reports: predominantly low-grade ocular (MIRV vs IC all grade 56% vs 9%; grade 3+ 14% vs 0%) and gastrointestinal events (MIRV vs IC all grade 70% vs 66%; grade 3+ 13% vs 15%). Compared with IC, MIRV was associated with lower rates of grade 3+ treatment-emergent AEs (42% vs 54%), serious AEs (24% vs 33%), and discontinuations due to TEAEs (9% vs 16%).
Conclusion: MIRV is the first treatment to demonstrate a statistically significant PFS, ORR and OS benefit in PROC compared to IC and demonstrates clinical benefit across subgroups. The efficacy data, along with the well-characterized safety profile, position MIRV as a new, standard of care for pts with FRα positive PROC. Trial information: NCT04209855
Moderator Commentary and Transition
SEMINAL: ENGOT-cx11/GOG-3047/KEYNOTE-A18: A RANDOMIZED, DOUBLE-BLIND, PHASE 3 STUDY OF PEMBROLIZUMAB PLUS CONCURRENT CHEMORADIOTHERAPY FOR HIGH-RISK LOCALLY ADVANCED CERVICAL CANCER
Abstract
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Introduction: Pembrolizumab has shown efficacy in patients with cervical cancer. The effect of chemoradiotherapy may be enhanced by immunotherapy. ENGOT-cx11/GOG-3047/KEYNOTE-A18 (NCT04221945) assessed pembrolizumab with concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer (LACC).
Methods: Pts with newly diagnosed, previously untreated, high-risk LACC (FIGO 2014 stage IB2-IIB with node-positive disease or stage III-IVA) were randomized to receive 5 cycles of pembrolizumab 200 mg or placebo Q3W + CCRT, then 15 cycles of pembrolizumab 400 mg or placebo Q6W. CCRT included 5 cycles (with optional 6th dose) of cisplatin 40 mg/m2 Q1W + EBRT then brachytherapy. Primary endpoints were PFS per RECIST v1.1 by investigator and OS.
Results: Pts were randomized to pembrolizumab+CCRT (n=529) or placebo+CCRT (n=531). At IA1 (January 9, 2023), median follow-up was 17.9 mo (range, 0.9-31.0). Pembrolizumab+CCRT showed a statistically significant improvement in PFS vs placebo+CCRT. 24-mo PFS was 67.8% with pembrolizumab + CCRT vs 57.3% with placebo+CCRT; median PFS was not reached in either group (HR=0.70 [95% CI, 0.55-0.89; P=0.0020]). With 103 events (42.9% maturity), addition of pembrolizumab to CCRT showed a favorable trend in OS (HR=0.73 [95% CI, 0.49-1.07]); these data have not crossed the boundary of statistical significance. Grade ≥3 TRAE incidence was 67.0% with pembrolizumab+CCRT group versus 60.0% with placebo+CCRT.
Conclusion/Implications: Pembrolizumab+CCRT showed a statistically significant and clinically meaningful improvement in PFS and a favorable trend in OS compared with placebo+CCRT in pts with high-risk LACC and had a manageable safety profile. These data suggest pembrolizumab+CCRT can be considered as a new standard of care for this population.
SEMINAL: Primary results from BEATcc (ENGOT-Cx10/GEICO 68-C/JGOG1084/GOG-3030), a randomised phase 3 trial of first-line atezolizumab combined with a platinum doublet and bevacizumab for metastatic (stage IVB), persistent or recurrent cervical cancer
Abstract
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Background: The open-label randomised phase 3 BEATcc academic trial (NCT03556839) evaluated atezolizumab (anti-PD-L1) combined with first-line chemotherapy (CT) + bevacizumab for metastatic (stage IVB), persistent or recurrent cervical cancer (R/M CC), irrespective of PD-L1 status. We report final progression-free survival (PFS) and interim overall survival (OS) results.
Methods: Patients (pts) with previously untreated measurable R/M CC not amenable to curative surgery/radiation were randomised 1:1 to standard therapy (cisplatin 50 mg/m2 or carboplatin AUC5 + paclitaxel 175 mg/m2 + bevacizumab 15 mg/kg) ± atezolizumab 1200 mg d1 q3w. Cycles were repeated until disease progression or unacceptable toxicity. Stratification factors were prior concomitant chemoradiation (yes vs no), histology (squamous cell carcinoma vs adenocarcinoma) and platinum agent (cisplatin vs carboplatin). Dual primary endpoints were investigator-assessed PFS per RECIST v1.1 and OS. Secondary endpoints included objective response rate (ORR), duration of response (DoR), time to first subsequent therapy (TFST), PFS2, and safety.
Results: Between Oct 2018 and Aug 2021, 410 pts were randomised. At the data cut-off (median follow-up 32.9 mo), median treatment duration was 8.5 vs 12.7 mo in the control vs atezolizumab arms, respectively; treatment was ongoing in 7% vs 23%, respectively. Both PFS and OS were statistically significantly improved with the addition of atezolizumab to CT + bevacizumab (Table). Secondary endpoints and subgroup analyses showed consistent results. Grade ≥3 adverse events (any cause) occurred in 75% vs 79% of the control and atezolizumab arms, respectively. Safety profiles were as expected with bevacizumab + platinum-based CT. Grade 1/2 diarrhoea, arthralgia, pyrexia and rash were increased with atezolizumab.
| Endpoint | CT + bevacizumab (n=204) | Atezolizumab + CT + bevacizumab (n=206) | |
| PFS | Events, n (%) | 166 (81) | 138 (67) |
| HR | 0.62 (0.49–0.78); p<0.0001 | ||
| Median, mo | 10.4 (9.7–11.7) | 13.7 (12.3–16.6) | |
| 2-year rate, % | 19 (14–25) | 36 (29–43) | |
| OS | Events, n (%) | 129 (63) | 105 (51) |
| HR | 0.68 (0.52–0.88); p=0.0046* | ||
| Median, mo | 22.8 (20.3–28.0) | 32.1 (25.3–36.8) | |
| 2-year rate, % | 49 (41–56) | 61 (53–67) | |
| TFST | Median, mo | 13.2 (12.0–14.3) | 19.0 (16.4–24.0) |
| HR | 0.60 (0.47–0.76) | ||
| PFS2 | Median, mo | 20.3 (17.8–22.3) | 25.8 (22.1–32.1) |
| HR | 0.61 (0.48–0.79) | ||
| ORR per RECIST v1.1, % | 72 (66–78) | 84 (79–89) | |
| DoR | n | 147 | 173 |
| Median, mo | 8.6 (8.0–10.6) | 13.6 (10.6–21.3) | |
| HR | 0.60 (0.46–0.78) | ||
| Brackets denote 95% CIs unless otherwise stated. HR = hazard ratio. *Statistically significant at interim analysis. | |||
Conclusions: Adding atezolizumab to first-line CT + bevacizumab for R/M CC significantly improved all efficacy outcomes. Median OS with atezolizumab + CT + bevacizumab exceeded 2.5 years.
SEMINAL: innovaTV 301/ENGOT-cx12/GOG-3057: A Global, Randomized, Open-Label, Phase 3 Study of Tisotumab Vedotin vs Investigator’s Choice of Chemotherapy in 2L or 3L Recurrent or Metastatic Cervical Cancer
Abstract
Abstract Body
Background: Tisotumab vedotin (TV) is an investigational antibody-drug conjugate directed to tissue factor. In the US, TV monotherapy received accelerated approval for the treatment of adult patients with recurrent or metastatic cervical cancer (r/mCC) with disease progression on or after chemotherapy. Here, innovaTV 301 (NCT04697628) study results are presented.
Methods: Eligible patients had r/mCC with disease progression on/after treatment with standard of care chemotherapy doublet ± bevacizumab ± anti-PD-(L)1 therapy, measurable disease per RECIST v1.1, and ECOG PS 0-1. Patients were randomized 1:1 to TV monotherapy or investigator's choice of topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed. The primary endpoint was OS. Key secondary endpoints included PFS and confirmed ORR by investigator.
Results: 502 patients were randomized (TV: 253; chemotherapy: 249); median survival follow-up was 10.8 months (95% CI, 10.3-11.6). Arms were balanced for demographics and disease characteristics, with 63.9% and 27.5% of patients receiving prior bevacizumab and prior anti-PD-(L)1 therapy, respectively. The TV arm had a 30% reduction in risk of death versus chemotherapy (HR 0.70; 95% CI 0.54-0.89; P=0.0038), with significantly longer median OS (11.5 months [95% CI 9.8-14.9] versus 9.5 months [95% CI 7.9-10.7]). PFS was superior in the TV versus chemotherapy arm (HR: 0.67 [95% CI, 0.54-0.82]; P<0.0001). The OS and PFS benefits in the prespecified subgroups were generally consistent with the ITT population. Confirmed ORR was 17.8% and 5.2% in the TV and chemotherapy arms, respectively (odds ratio: 4.0; 95% CI, 2.1-7.6; P<0.0001). Most patients experienced ≥1 treatment-related adverse event (TV: 87.6% [grade ≥3: 29.2%] versus chemotherapy: 85.4% [grade ≥3: 45.2%]). AEs were consistent with the known TV safety profile.
Conclusions: In the phase 3 innovaTV 301 study, TV showed a statistically significant and clinically meaningful improvement in OS, PFS, and ORR versus chemotherapy, with a manageable and tolerable safety profile in patients with 2L/3L r/mCC.
Previously presented in part at ESMO 2023, “LBA9: innovaTV 301/ENGOT-cx12/GOG-3057: A Global, Randomized, Open-Label, Phase 3 Study of Tisotumab Vedotin vs Investigator’s Choice of Chemotherapy in 2L or 3L Recurrent or Metastatic Cervical Cancer ”, Ignace Vergote et al. - Reused with permission