NEOADJUVANT

THERAPY IN CA
OVARY
Dr Arun Warrier
Medical Oncologist
Systemic options- Neoadjuvant

■ Chemotherapy-IV/Dose Dense/ Intraperitoneal

■ Bevacizumab
■ HIPEC
■ PARP inhibitors
Evolution of drugs over 50 years
ESMO GUIDELINES
Which chemotherapy?
BEVACIZUMAB
PFS better- No effect on OS
Neoadj Bev- Published trials(2018)
GEICO1202/NOVA ANTHALYA

Surgical resection rate- Optimal 63 % v/s 65% 58 % v/s 47%

Surgical feasibility rate 88 v/s 66 % 87 v/s 60 %

Median PFS 20 months in both

Numbers 95 70
RATIONALE FOR IP
■ Largest volume of disease in advanced ovarian cancer is frequently
within the peritoneal cavity, and treatment can be focused there with IP
treatment.
■ Pharmacologic data show that, compared with IV treatment, IP
administration will result in a several-fold increase in drug concentration
in the abdominal cavity
■ Drug clearance from the peritoneal cavity is significantly slower than
from the vascular compartment, resulting in prolonged duration of drug
exposure.
■ GOG 114(2001)
■ GOG 172 (2006)
Advantage of IV/IP over IV chemotherapy extends beyond 10 years and that
survival improved with an increasing number of IP cycles delivered
■ GOG 252( 2019)
Compared with the IV carboplatin reference arm, the duration of PFS was
not significantly increased with either IP regimen when combined with
bevacizumab and was better tolerated than IP cisplatin
■ OV21/PETROC
Provided data to support the use of an IV/IP carboplatin-based regimen after
NACT.
HIPEC
EFFICACY
Published RCTs
INDIAN SOCIETY OF PERITONEAL SURFACE MALIGNANCIES

www.ispsm.org
Registered Body by Registrars of Society
 PARAMETERS n %

Age distribution (in %)

a.<40 years 172 11.61%
b.40-60 years 1047 71.26%
c.>60 years 251 17.12%
Type
Upfront 348 23.3%
Interval 685 46.6%
Recurrent 437 30%
 Interval Group - Comparison of Present study with recent published literature

N FIGO Follow up CC0 Morbidity Mortality Median OS Median PFS

(months) (%) (months) (months)
Interval HIPEC 122 III 56.4 68 28 0 48 15
Van Driel [*]
Lim [**] 92 III/IV 32.6 - - 0 54 20

Present 685 III 63 92% 27.3% 2.5% 58 30

*van Driel WJ, Koole SN, Sonke GS. Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer. N Engl J Med. 2018 Apr 5;378(14):1363-1364
**Myong Cheol Lim, Suk-Joon Chang, Heong Jong Yoo, Byung-Ho Nam, Robert Bristow, and Sang-Yoon Park.
Randomized trial of hyperthermic intraperitoneal chemotherapy (HIPEC) in women with primary advanced peritoneal, ovarian, and tubal cancer. Journal of Clinical
Oncology 2017 35:15_suppl, 5520-5520
Conclusions- HIPEC
PIPAC
HIPEC IN RELAPSE
TARGETED THERAPY
Neoadjuvant PARPi- KNOWN

■ Gorodnova et al. showed that 34% patients with germline

mutations had complete clinical response compared to 4% of
wild type patients
■ Pathological complete response was observed in 46% of
women with germline mutations in BRCA1/2 compared to
24% of patients without such mutations
UNKNOWN

■ NACT-IDS group, expression of RAD51 was independently

associated with worse outcomes, while in the PDS group,
overexpression of three genes (NBN, FANCF and RAD50)
correlated with better prognosis
■ Therefore, the predictive and prognostic role of molecular
alterations in HRR genes need to be further evaluated.
Immune milieu of Ovarian cancer
NACT and immune activation
■ Effect of NACT on immune activation in stage III/IV tubo-ovarian
HGSOC and its association to response to treatment
■ patients with a good response to NACT had reduced T-cell infiltration
and more pronounced T-cell activation compared to poor responders.
■ NACT also induced activation of CD4+ T cells, CD8+ T cells and
CD45RO+ memory cells in omental metastases.
■ Levels of the immune-checkpoint molecules PD-1 and CTLA4 on
CD4+ and CD8+ T cells remained high after NACT.
■ A significant increase in the levels of PD-L1 on tumor infiltrating
immune cells was reported
■ Systemic levels of three key inflammatory cytokines, IL6, IL8 and TNF
were significantly raised after NACT.
Clinical impact
■ Stromal TILs (sTILs) levels were prognostic at diagnosis and remained
prognostic post-NACT
■ An overall increase in median stromal sTILs density from 20% to 30%
was seen after NACT in patients with epithelial ovarian cancer.
■ Post-NACT, sTIL density had a predictive role for platinum-free interval
(PFI), with patients with a PFI >6 months having significantly higher
post-NACT sTIL density.
■ 33% of patients showed increasing intraepithelial TILs (ieTILs) density
following NACT.
■ Proportion of tumours with PD-L1-positive immune cells was 30%
(15/50) pre-NACT and 53% (27/51) post-NACT (p=0.026).
AdoRN- 2021
■ AdoRN trial were presented at the 52nd Annual Meeting on Women’s
Cancer
■ The investigators evaluated atezolizumab in combination with NACT
(paclitaxel 80 mg/m2 D1/8/15 + carboplatin AUC 6 D1 + atezolizumab
1200 mg D1, every 3 weeks for 3 cycles) followed by IDS for patients
with newly diagnosed advanced-stage epithelial ovarian cancer.
■ NACT with atezolizumab succeeded optimal cytoreduction in 86% of
patients [R0 (53%), R1 (33%)].
■ Tumor and blood biomarkers results, which are expected, could identify
potential candidates who may benefit from atezolizumab front-line
therapy.
■ No new safety signals
■ Immunotherapy and NACT seem to have a synergistic role
Immuno + Bev

■ Ovarian tumors associated with increased vascular

endothelial growth factor production
■ Vascular endothelial growth factor blockade may promote
T-cell infiltration into the tumor bed and reduce
immunosuppression within the tumor microenvironment
■ Combine immunotherapeutic and antiangiogenic
strategies??
ImGyn 2021

■ 1,301 patients were enrolled.

■ The median progression-free survival was 19.5 versus 18.4 months
with atezolizumab versus placebo, respectively (hazard ratio, 0.92;, in
the intention-to-treat population
■ 20.8 versus 18.5 months, respectively (hazard ratio, 0.80; 95% CI,
0.65 to 0.99; P = .038), in the PD-L1–positive population.
■ The interim (immature) overall survival results showed no significant
benefit from atezolizumab.