To see the future, gynecological tumor treatment ushered in a "window of opportunity" 2021 ASCO gynecological tumor special

*Only for medical professionals to read the reference article to understand the 2021ASCO gynecology major research
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 The 2021 American Society of Clinical Oncology (ASCO) annual meeting was successfully held in the form of an online virtual conference from June 4 to 8.
As an international oncology conference with great influence, 2021ASCO announced blockbuster research in many cancer fields , Has also attracted the attention of oncologists and scholars at home and abroad
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In this "complex tumor expert group take you to see the 2021 ASCO-Gynecological Oncology Special", Professor Wu Xiaohua and Dr.
Han Xiaotian from the Fudan University Affiliated Tumor Hospital were invited to live online to interpret several important studies in the field of 2021ASCO Gynecological Oncology
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 Scan the code to watch the wonderful live replay Phase III OUTBACK study: Adding adjuvant chemotherapy after standard radiotherapy and chemotherapy can not improve the survival outcome of patients with locally advanced cervical cancer.
Simultaneous radiotherapy and chemotherapy are the standard treatment options for locally advanced cervical cancer
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However, there is still a large proportion of patients who will relapse or metastasize after treatment, leading to death
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Past data suggests that giving more chemotherapy after radiotherapy may help change clinical practice
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In order to systematically verify the effectiveness of this program, the American Gynecological Oncology Group (GCIG) initiated the OUTBACK study to explore whether adding adjuvant chemotherapy after standard radiotherapy and chemotherapy can improve the survival of patients with locally advanced cervical cancer
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At this ASCO conference, the latest results of the OUTBACK research were selected as Late-breaking Abstract (LBA) (abstract number: LBA3)
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The OUTBACK study is an international multi-center, randomized, phase III clinical study.
The participating organizations/countries include ANZGOG (Australia and New Zealand), NRG (United States, Saudi Arabia, Canada, China) and Singapore
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The study design is shown in Figure 1.
The enrolled patients were locally advanced cervical cancer (FIGO 2008 IB1 stage and lymph node positive, IB2, II, IIIB or IVA stage)
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According to the stratification factors such as lymph node status, participating location, FIGO staging, age, and planned expanded field radiotherapy, the enrolled patients were randomly assigned to the standard cisplatin radiotherapy and chemotherapy group (CRT group) or standard cisplatin radiotherapy and chemotherapy + 4 cycles of carboplatin / Paclitaxel adjuvant chemotherapy group (CRT+ACT group)
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The primary endpoint of the study was the 5-year overall survival (OS) rate; secondary endpoints included progression-free survival (PFS), adverse events (AE), and disease recurrence patterns
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Figure 1.
The results of the OUTBACK study design showed that a total of 919 patients were included for survival analysis from April 2011 to June 2017, of which 463 cases were in the CRT+ACT group and 456 cases were in the CRT group
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In the CRT+ACT group, 361 patients (78%) received adjuvant chemotherapy, with a median follow-up time of 60 months (IQR 45-65 months)
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The 5-year OS rate of CRT+ACT group and CRT group (72%vs.
71%, HR=0.
91, 95%CI 0.
70-1.
18, P=0.
91) (Figure 2) and 5-year PFS rate (63%vs.
61) %, HR=0.
87, 95%CI 0.
70-1.
08, P=0.
61) (Figure 3), there was no significant difference
.

Figure 2.
OS results of the OUTBACK study Figure 3.
Subgroup analysis of the PFS results of the OUTBACK study showed that patients younger than 60 years old can benefit from CRT+ACT treatment, while patients over 60 years old can benefit more from standard radiotherapy and chemotherapy alone (Picture 4)
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Figure 4.
The results of the subgroup analysis of the OUTBACK study.
In terms of safety, within 1 year after randomization, the incidence of grade 3 to 5 AEs in the CRT+ACT group receiving adjuvant chemotherapy was 81%, and that of the control group was 62%
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After randomization for more than 1 year, there is no evidence that there is a difference in AE between the two groups
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The disease recurrence patterns of the two groups of patients were also similar
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The results of this study indicate that patients with locally advanced cervical cancer receiving adjuvant chemotherapy after standard cisplatin radiotherapy and chemotherapy cannot improve the survival benefit
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Dr.
Han Xiaotian commented, “This is a large-scale, global multi-country/center clinical study.
Although the results are negative, they are very meaningful
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This study also has some limitations, such as randomization in CRT Previously, many patients who should be enrolled in adjuvant chemotherapy did not undergo adjuvant chemotherapy; and most of the patients were in high-income countries, which may have an impact on the results
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On the other hand, the researchers used carboplatin + cisplatin adjuvant chemotherapy However, the previous positive results used the cisplatin + gemcitabine regimen.
Whether adjuvant chemotherapy will affect the results is also worth pondering
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"Phase II NeoPembrOv study: Adding pembrolizumab during neoadjuvant chemotherapy can improve advanced high-grade serous The complete resection rate of cancer, but no PFS benefit.
Multiple clinical studies have proved that in patients with stage III/IV ovarian cancer, the efficacy of neoadjuvant chemotherapy is not inferior to the initial cytoreductive surgery (PDS) treatment
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The 2018 ESMO/ESGO guidelines have recommended neoadjuvant chemotherapy as a treatment option for patients with initial incomplete resection
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However, only 50% to 65% of patients can complete complete tumor resection after neoadjuvant chemotherapy
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How to improve the clinical outcome of patients? Neoadjuvant therapy combined with PD-(L)1 inhibitor is a potential solution
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The results of a NeoPembrOv study of this type of exploration (Abstract No.
5500) was announced at this ASCO conference
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The NeoPembrOv study (NCT03275506) is a multicenter, open-label, non-controlled, randomized phase II clinical trial, which aims to explore the initial unresectable FIGO stage IIIC/IV ovarian, fallopian tube or peritoneal advanced high-grade serous carcinoma (HGSC ) In patients, whether the addition of pembrolizumab (P) during neoadjuvant carboplatin-paclitaxel chemotherapy (CP) can increase the maximum tumor reduction rate [by the complete resection rate (CRR) after intermediate cytoreduction (IDS) Evaluation]
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The patients were randomly assigned to receive 4 cycles of CP±P at 2:1 and then underwent IDS
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After IDS, all patients received postoperative chemotherapy (2 to 4 cycles) and selective bevacizumab treatment for 15 months, ±P as maintenance treatment, and the total treatment duration was 2 years
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Randomization was based on treatment center, FIGO staging, bevacizumab use plan after IDS, and lesion size (<5cm/>5cm)
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CRR when the primary endpoint is IDS
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The secondary study endpoints were safety, surgical incidence, ORR, PFS and OS
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Figure 5.
The results of the NeoPembrOv study design showed that a total of 91 patients were randomly divided into groups, 80 patients (88%) received bevacizumab combined with CP treatment, and then received bevacizumab ± P for maintenance treatment
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In the CP+P group (n=61), 58 patients (95%) received IDS, 78% of them completed complete resection, and the final CRR was 74%, which was statistically superior to the pre-set hypothesis
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CP group (n=30) CRR was 70% (29/30 patients received IDS)
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After 4 cycles of chemotherapy, 41 (71%) and 17 (58%) patients in the CP+P group and the CP group respectively completed complete resection
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Before IDS, the CP+P group had a higher ORR (76% vs.
61%) than the CP group, but it did not translate into a PFS benefit.
The 18-month PFS rates of the CP+P group and the CP group were 61%, respectively And 57%, there is no significant difference (Figure 6)
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Figure 6.
Results of NeoPembrOv study PFS.
In terms of safety, the incidence of AEs ≥3 in the CP+P group and CP group were 75% and 67%, respectively, mainly blood, lymph, gastrointestinal and vascular diseases
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Postoperative AEs (mainly infections, vascular and gastrointestinal reactions) occurred in 20% and 13% of patients in the CP+P and CP groups, respectively
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There was no difference in the number of deaths due to treatment between the two groups
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The results of this study indicate that in patients with initial unresectable stage IIIC/IV HGSC, the addition of pembrolizumab during neoadjuvant chemotherapy can increase the complete resection rate, but this benefit does not translate into a survival benefit
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The current survival data and translational studies including PD-L1 status are underway in order to better evaluate the effect of pembrolizumab
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Professor Wu Xiaohua said, “This is a very interesting study.
We should focus on three points: First, does immunotherapy have an effect on advanced ovarian cancer? Phase III IMagyn050 study (atilizumab combined with bevacizumab, Paclitaxel and carboplatin in the first-line treatment of patients with advanced ovarian cancer) failed to achieve the primary endpoint, and did not significantly improve the PFS of patients compared with the control group
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The negative results of the IMagyn050 study have already made a certain answer
.
The
second point is that the purpose of ovarian cancer treatment is Survival rate
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So far, neoadjuvant chemotherapy is still controversial and cannot improve survival
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The third point is that the biological behavior of the tumor, the patient's physical condition, and surgical skills will all affect the R0 rate of surgery
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We cannot change the biological behavior of the tumor and the patient's status, but we can improve the surgical skills to increase the R0 rate
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"Phase IIb VITAL study subgroup analysis: The first-line use of Vigil immunotherapy as a maintenance treatment for homologous recombination to repair normal stage III/IV ovarian cancer has significant clinical benefits and is well tolerated.
VITAL study (NCT02346747) is a randomized , Double-blind, placebo-controlled, phase IIb clinical study
.
The
study included 92 newly diagnosed stage III/IV ovarian cancer patients with clinical complete remission (CR) after first-line surgery and chemotherapy
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Patients were randomized to receive up to 12 doses of vigil or Placebo treatment or until the disease progresses to evaluate the effectiveness and safety of Gemogenovatucel-T (Vigil) (an autologous tumor cell vaccine) in the maintenance treatment of ovarian cancer
.
The
primary endpoint of the study is the RFS evaluated by a blind independent center
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VITAL The main analysis results of the study showed that compared with placebo, Vigil maintenance treatment after first-line platinum chemotherapy can make patients with advanced high-grade ovarian cancer have a better recurrence-free survival (RFS) benefit (11.
5 months vs.
8.
4 months) ; HR = 0.
69; 90% CI , 0.
44-1.
07; p = 0.
078) ( FIG.
7), and the wild-type BRCA benefit patients with more significant (the HR = 0.
51; 90% CI, 0.
30-0.
88; P = 0.
020)
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in At this ASCO meeting, the researchers reported the analysis results of the normal homologous recombination repair (HRP) subgroup (Abstract No.
5502)
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The results of the study showed that 62 BRCA wild-type patients were tested for homologous recombination defect (HRD) status (determined by myChoice-CDx test, HRD score <42 was HRP), 45 patients were HRP, and 17 patients were HRD
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From the start of randomization, the median RFS (10.
6 months vs.
5.
7 months) and OS (not yet reached vs.
5.
7 months) of HRP patients in the Vigil treatment group (n=25) were compared with those in the placebo group (n=20).
.
26.
9 months) has a significant improvement (Figure 8)
.

The latest follow-up data showed that the 2-year OS rate (92% vs.
55%, P=0.
002) and 3-year OS rate (70% vs.
40%, P=0.
019) of HRP patients in the Vigil treatment group were significantly better than those of comfort Agent group (Figure 9)
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In terms of safety, no HRP patients in the Vigil treatment group had treatment-related grade 3 or higher AEs
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Figure 7.
The results of RFS and OS of the VITAL study in the overall population.
Figure 8.
The results of RFS and OS of the VITAL study HRP subgroup.
Figure 9.
The latest follow-up results of the VITAL study HRP subgroup.
The results of the study indicate that the first-line use of vigil immunotherapy for stage III/IV ovarian cancer Maintenance therapy is well tolerated, and BRCA wild-type patients and HRP patients have significant clinical benefits
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Dr.
Han Xiaotian pointed out, “This phase IIb study has obtained very good positive results, but further phase III clinical studies are needed to verify its results
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”