For Doctors — Oncology Resources & Guidelines

Guideline Summaries

Key updates from NCCN, ESMO, ASCO & ICMR for gynecological cancers — distilled into actionable summaries.

NCCN Guidelines (v2025)

Cervical Cancer

First-line recurrent/metastatic: Pembrolizumab + cisplatin/carboplatin + paclitaxel ± bevacizumab — Category 1 for PD-L1 CPS ≥1 (KEYNOTE-826)
Second-line: Tisotumab vedotin — Category 1 preferred option after prior chemotherapy (innovaTV 301, FDA traditional approval April 2024)
Locally advanced (IB2–IVA): Concurrent cisplatin-based chemoradiation + brachytherapy remains standard
Sentinel lymph node mapping incorporated for early-stage surgical staging

Ovarian Cancer

BRCA-mutated maintenance: Olaparib (SOLO-1) — Category 1; 7-year mPFS 56.0 vs 13.8 months
HRD-positive maintenance: Olaparib + bevacizumab (PAOLA-1) or niraparib (PRIMA) — Category 1
All-comer maintenance: Niraparib — Category 1 regardless of HRD/BRCA status (PRIMA)
KRAS-mutated LGSOC: Avutometinib + defactinib (FDA approved May 2025, RAMP-201)

Endometrial Cancer

First-line advanced/recurrent (ALL patients): Pembrolizumab + carboplatin/paclitaxel (KEYNOTE-868) OR Dostarlimab + carboplatin/paclitaxel (RUBY) — both Category 1
dMMR patients: Durvalumab + carboplatin/paclitaxel (DUO-E) — Category 1
Molecular testing: Universal reflex MMR/MSI and POLE testing — Category 1
Second-line: Lenvatinib + pembrolizumab (KEYNOTE-146) — Category 1 regardless of MMR status

ESMO/ESGO/ESTRO/ESP Guidelines

Endometrial Cancer — ESGO-ESTRO-ESP 2025 Update

Concin N, et al. Lancet Oncol. 2025;26(8):e423–e435

Molecular classification is now mandatory — four subtypes drive treatment: POLE-ultramutated (excellent prognosis), MMR-deficient (immunotherapy benefit), p53-abnormal (aggressive), NSMP (variable)
Sentinel lymph node mapping as preferred surgical approach
Immunotherapy integrated into advanced/recurrent disease management

Ovarian Cancer — ESGO-ESMO-ESP Consensus 2024

Ledermann JA, et al. Ann Oncol. 2024;35(3):248–266

Universal germline BRCA1/2 testing for all newly diagnosed ovarian cancer
HRD testing (tumor-based) for all high-grade serous/endometrioid EOC
First-line PARP inhibitor maintenance based on BRCA/HRD status
Pan-Asia adapted ESMO guideline (2025) addresses resource-stratified settings relevant to Indian practice

ASCO Guidelines

BRCA/HRD Testing: All newly diagnosed ovarian cancer — germline BRCA1/2 first, somatic if germline negative, HRD testing for maintenance decisions
PARP Inhibitors: Olaparib (BRCA-mutated), niraparib (all advanced), or olaparib + bevacizumab (HRD-positive) as maintenance
Cervical Cancer: Pembrolizumab + chemotherapy as standard first-line for PD-L1 CPS ≥1
Endometrial Cancer: Pembrolizumab or dostarlimab + chemotherapy for advanced disease; universal MMR/MSI testing

ICMR / National Cancer Grid (India)

NCG treatment guidelines align with NCCN, adapted for Indian resource settings
Cisplatin-based regimens preferred where cost is a factor
Bevacizumab biosimilars widely incorporated in NCG-recommended protocols
Cervavac — India's indigenous quadrivalent HPV vaccine (WHO-prequalified 2024) — part of ICMR prevention recommendations
PARP inhibitors (olaparib, niraparib) available through specialty centers in India
CDSCO has approved pembrolizumab, dostarlimab, olaparib, niraparib, and tisotumab vedotin

Drug Updates

Recent approvals and key trial data in gynecological oncology.

Checkpoint Inhibitors

Pembrolizumab (Keytruda) — Anti-PD-1

Cervical Cancer (KEYNOTE-826): Pembro + chemo ± bevacizumab. PD-L1 CPS ≥1: mOS 28.6 vs 16.5 months (HR 0.60). FDA approved Oct 2021.

Endometrial Cancer (KEYNOTE-868): Pembro + carboplatin/paclitaxel for ALL patients. dMMR: mPFS NR vs 6.5m (HR 0.30); pMMR: mPFS 11.1 vs 8.5m (HR 0.60). FDA approved June 2024.

Platinum-resistant Ovarian (KEYNOTE-B96): Pembro + paclitaxel ± bevacizumab for PD-L1 CPS ≥1. mOS 18.2 vs 14.0 months (HR 0.76). FDA approved Feb 2026.

Dostarlimab (Jemperli) — Anti-PD-1

RUBY Trial — Endometrial Cancer: Dostarlimab + carboplatin/paclitaxel → dostarlimab maintenance (up to 3 years). Overall: mOS 44.6 vs 28.2 months (HR 0.69). First immunotherapy showing OS benefit across ALL endometrial cancer patients. FDA expanded to all EC August 2024.

Durvalumab (Imfinzi) — Anti-PD-L1

DUO-E Trial — dMMR Endometrial Cancer: Durvalumab + carboplatin/paclitaxel → durvalumab maintenance. dMMR: mPFS NR vs 7.0m (HR 0.42). FDA approved June 2024. Note: Approval restricted to dMMR patients only.

PARP Inhibitors

Olaparib (Lynparza)

SOLO-1 (BRCA-mutated EOC): First-line maintenance. 7-year mPFS: 56.0 vs 13.8 months (HR 0.33). ~50% progression-free at 7 years — potential "functional cure" in a subset.

PAOLA-1 (HRD-positive EOC): Olaparib + bevacizumab maintenance. HRD+: mPFS 37.2 vs 17.7 months (HR 0.33). Updated OS data (2024) confirms benefit in HRD+/BRCA-mutated patients.

Niraparib (Zejula)

PRIMA (all advanced EOC): Biomarker-agnostic maintenance. HRD+: mPFS 21.9 vs 10.4m (HR 0.43); Overall: mPFS 13.8 vs 8.2m (HR 0.62). Only PARP inhibitor approved for all patients regardless of BRCA/HRD. Individualized dosing (200mg or 300mg) reduces hematological toxicity. Available in India through specialty centres.

ADCs & Novel Agents

Tisotumab Vedotin (Tivdak) — Anti-TF ADC

innovaTV 301 — Cervical Cancer: First ADC approved in cervical cancer. mOS 11.5 vs 9.5m (HR 0.70); mPFS 4.2 vs 2.9m. Traditional FDA approval April 2024. Key AE: Ocular toxicity — requires prophylactic vasoconstrictor eye drops and ophthalmic monitoring. Active after prior immunotherapy.

Avutometinib + Defactinib — MEK + FAK Inhibitors

RAMP-201 — KRAS-mutated LGSOC: First approval for molecular subtype of LGSOC. ORR 44%. FDA accelerated approval May 2025. KRAS mutation testing required (companion diagnostic).

Biosimilars in India

Biologic	Indian Biosimilars	Oncology Use
Bevacizumab	Bevatas (Intas), Abevmy (Mylan)	Cervical & ovarian cancer (1st-line + maintenance)
Trastuzumab	Hertraz (Mylan), Biceltis (Biocon)	HER2+ uterine serous carcinoma
Pegfilgrastim	Fulphila (Mylan)	G-CSF support during chemotherapy
Filgrastim	Multiple Indian generics	G-CSF support (widely available)

Bevacizumab biosimilars are widely used in NCG-recommended protocols, providing significantly lower cost access compared to originator products.

Biomarker Testing

Essential biomarkers in gynecological oncology — testing, interpretation, and clinical implications.

MMR/MSI Testing

Method: IHC (MLH1, MSH2, MSH6, PMS2) or PCR/NGS-based MSI analysis
Endometrial cancer: ~25-30% dMMR/MSI-H. Mandatory reflex testing at diagnosis. Triggers Lynch syndrome screening.
Clinical impact: Predicts benefit from pembrolizumab, dostarlimab, durvalumab in advanced EC
Ovarian: ~20% in non-serous histotypes; responds to pembrolizumab (tumor-agnostic approval)

PD-L1 Testing

Assay: IHC 22C3 pharmDx (Agilent) — score by CPS (Combined Positive Score), not TPS
Cervical cancer: CPS ≥1 required for pembrolizumab + chemo (KEYNOTE-826); CPS ≥10 shows maximal OS benefit
Platinum-resistant ovarian: CPS ≥1 for pembrolizumab + paclitaxel (KEYNOTE-B96)
Endometrial: Less critical — benefit extends to unselected patients

HRD / BRCA Testing

Components: BRCA1/2 mutation status (germline + somatic) + genomic scar score (GIS/LOH)
Who to test: All newly diagnosed high-grade serous/endometrioid EOC
Sequence: Germline BRCA first → somatic if germline negative
HRD-positive: BRCA1/2-mutated OR GIS ≥42 → olaparib (SOLO-1), olaparib + bevacizumab (PAOLA-1), niraparib (PRIMA)
India: Myriad myChoice CDx limited availability; FoundationOne CDx through reference labs; several Indian labs offer in-house LOH testing

Endometrial Cancer Molecular Classification

Subtype	Prevalence	Prognosis	Treatment Impact
POLE-ultramutated	~10%	Excellent	Consider de-escalation of adjuvant therapy
MMR-deficient	~25%	Intermediate	Best biomarker for immunotherapy benefit
p53-abnormal	~15%	Poor	Aggressive treatment; HER2 testing in serous
NSMP	~50%	Variable	ER/PR guides hormonal therapy decisions

Prognostic hierarchy (best to worst): POLE > MMRd > NSMP > p53-abnormal. ESGO-ESTRO-ESP 2025 mandates molecular classification where resources permit.

CME — Landmark Trials

Key clinical trials shaping gynecological oncology practice — structured for teaching and quick reference.

KEYNOTE-826 — Cervical Cancer

Monk BJ, et al. NEJM 2021; Final OS: JCO 2023

Phase III, n=617. Pembrolizumab + chemo ± bevacizumab vs placebo + chemo. PD-L1 CPS ≥1: mOS 28.6 vs 16.5m (HR 0.60). First anti-PD-1 approval in first-line cervical cancer. PD-L1 CPS (not TPS) is the relevant biomarker. Benefit seen with and without bevacizumab.

RUBY Trial — Endometrial Cancer

Mirza MR, et al. NEJM 2023

Phase III, n=494. Dostarlimab + carboplatin/paclitaxel → dostarlimab maintenance (up to 3 years). Overall: mOS 44.6 vs 28.2m (HR 0.69). dMMR: substantially superior (HR ~0.28). First immunotherapy trial showing OS benefit across ALL endometrial cancer histologies. Paradigm shift: pMMR patients also benefit.

KEYNOTE-868 / NRG-GY018 — Endometrial Cancer

Eskander RN, et al. NEJM 2023

Phase III, n=810. Pembrolizumab + carbo/taxol → pembro maintenance. dMMR: mPFS NR vs 6.5m (HR 0.30); pMMR: mPFS 11.1 vs 8.5m (HR 0.60). Both p<0.0001. Confirms immunotherapy benefit in pMMR — the major paradigm shift. Shorter maintenance (~2 years) vs RUBY's 3 years.

SOLO-1 — Ovarian Cancer (Olaparib)

Moore K, et al. NEJM 2018; 7-year follow-up NEJM 2023

Phase III, n=391 BRCA-mutated advanced EOC. Olaparib maintenance for 2 years. 7-year mPFS: 56.0 vs 13.8m (HR 0.33). ~50% progression-free at 7 years. Unprecedented durable responses — potential "functional cure" in a subset of BRCA-mutated patients.

PRIMA — Ovarian Cancer (Niraparib)

González-Martín A, et al. NEJM 2019

Phase III, n=733. Niraparib maintenance for all advanced EOC. HRD+: mPFS 21.9 vs 10.4m (HR 0.43); Overall: 13.8 vs 8.2m (HR 0.62). Only PARP inhibitor approved regardless of BRCA/HRD status. Individualized dosing based on weight and platelet count reduces toxicity without compromising efficacy.

PAOLA-1 — Ovarian Cancer (Olaparib + Bevacizumab)

Ray-Coquard I, et al. NEJM 2019; Updated 2024

Phase III, ~806 patients. Olaparib + bevacizumab maintenance. HRD+: mPFS 37.2 vs 17.7m (HR 0.33). HRD testing is mandatory — HRD-negative patients do NOT benefit from adding olaparib. Updated 2024 data confirms OS benefit in HRD+/BRCA-mutated.

innovaTV 301 — Cervical Cancer (Tisotumab Vedotin)

Coleman RL, et al. Lancet 2023

Phase III, n=502. Tisotumab vedotin vs investigator's choice chemotherapy. mOS 11.5 vs 9.5m (HR 0.70); ORR 17.8% vs 5.2%. First ADC approved in cervical cancer. Ocular toxicity is unique — requires prophylactic vasoconstrictor eye drops and ophthalmic monitoring before each cycle. Active after prior immunotherapy.

Content is for medical professional reference only. Guidelines and approvals are current as of early 2025. Always verify with primary sources before clinical application.

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