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Platinum-sensitive ovarian cancer is disease that responded to carboplatin and either has not relapsed or relapses more than six months after the last dose. It is treated with further platinum chemotherapy, sometimes repeat surgery, and above all with maintenance PARP inhibitors, which keep BRCA-mutant tumours away for years and have raised long-term survival.
Platinum sensitivity is a clinical state rather than a histology. A tumour that shrinks on carboplatin-paclitaxel and stays away for more than six months after the last cycle is likely to respond to platinum again, and the longer the platinum-free interval the better the response; most high-grade serous and endometrioid cancers begin in this state and drift towards resistance with each relapse. Biologically, sensitivity tracks homologous recombination deficiency: BRCA1 or BRCA2 mutation, found in about a fifth of high-grade serous tumours, and other defects that together mark about half, cannot repair the DNA crosslinks platinum causes, and the same defect makes them vulnerable to PARP inhibition. Germline and somatic BRCA testing and HRD testing are therefore standard at diagnosis.
Maintenance after first-line chemotherapy is the setting with the clearest gains. SOLO-1 gave two years of olaparib to women with BRCA-mutant tumours in response to platinum and cut the hazard of progression to 0.30; at seven years 67.0 percent were alive against 46.5 percent with placebo, a hazard ratio for death of 0.55 and the first sign that maintenance changes survival rather than delaying relapse. PRIMA extended niraparib to all comers with a progression-free survival gain from 8.2 to 13.8 months overall and from 10.4 to 21.9 months in HRD-positive tumours, though its final overall survival analysis showed no difference. PAOLA-1 added olaparib to bevacizumab maintenance and, in HRD-positive tumours, extended progression-free survival from 17.7 to 37.2 months with five-year survival of 65.5 percent against 48.4 percent. ATHENA-MONO confirmed the class with rucaparib. Which drug, whether to add bevacizumab, and whether HRD-negative tumours gain enough to justify treatment are decided by the tests.
At platinum-sensitive relapse, DESKTOP III showed that secondary cytoreductive surgery in women selected by a positive AGO score, complete resection at first surgery, good performance status and no ascites, extended median survival from 46.0 to 53.7 months when complete resection was achieved. Chemotherapy is a platinum doublet, carboplatin with pegylated liposomal doxorubicin, gemcitabine or paclitaxel, with bevacizumab in patients who have not had it, followed by PARP inhibitor maintenance if none was given before. Trials in relapse showed that PARP inhibitor maintenance after a later-line response delayed progression but did not improve survival in non-BRCA tumours and regulators narrowed those labels in 2022 and 2023, so the main benefit is now taken in the first line. Second PARP inhibitor exposure after progression, HRD-restoring reversion mutations and circulating tumour DNA to guide the duration of maintenance are the current research questions.
Most advanced ovarian cancers respond to first-line platinum, and the majority of relapses occur more than six months after the last platinum dose; this state covers the largest group of women on treatment and is where PARP inhibitor maintenance has changed the natural history.
Most high-grade ovarian cancers begin at the tip of the fallopian tube; endometrial cancer lines the uterus, cervical cancer starts at the transformation zone; each drains to a different node group.
Same organ: Adenosquamous carcinoma of the cervix, Small cell neuroendocrine carcinoma of the cervix, Bartholin gland carcinoma, Vulvar melanoma, Vaginal melanoma, High-grade serous ovarian cancer, Low-grade serous ovarian cancer, Clear cell ovarian cancer, Mucinous ovarian cancer, Adult granulosa cell tumour of the ovary, Ovarian cancer, Endometrial cancer, Cervical cancer, Vulvar cancer, Gestational trophoblastic neoplasia, Uterine sarcoma, Vaginal cancer, POLE-ultramutated endometrial cancer, Mismatch-repair-deficient endometrial cancer, p53-abnormal endometrial cancer, including uterine serous carcinoma, Endometrial cancer with no specific molecular profile, Advanced or recurrent endometrial cancer, Uterine carcinosarcoma, Early cervical cancer and fertility-sparing surgery, Locally advanced cervical cancer, Recurrent or metastatic cervical cancer, Platinum-resistant ovarian cancer, HPV-associated vulvar squamous cell carcinoma, HPV-independent vulvar squamous cell carcinoma (p53-mutant), Vaginal squamous cell carcinoma (HPV-associated), Vaginal adenocarcinoma (including DES-associated clear cell adenocarcinoma), Low-risk gestational trophoblastic neoplasia (FIGO score 0 to 6), High-risk gestational trophoblastic neoplasia (FIGO score 7 or more, including ultra-high-risk), Placental-site trophoblastic tumour and epithelioid trophoblastic tumour
Olaparib for two years (SOLO-1), or olaparib with bevacizumab (PAOLA-1); niraparib as an alternative.
Olaparib plus bevacizumab (PAOLA-1) or niraparib (PRIMA) after HRD testing.
Niraparib (PRIMA, smaller benefit) or bevacizumab; observation is reasonable after discussion.
Secondary cytoreduction in AGO-score-positive patients (DESKTOP III), then carboplatin doublet with pegylated liposomal doxorubicin, gemcitabine or paclitaxel, bevacizumab if not previously given, and PARP inhibitor maintenance if PARP-naive.
Platinum doublet; PARP rechallenge has limited benefit; trials of ATR, WEE1 and next-generation PARP1-selective inhibitors.
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Secondary cytoreduction is recommended for AGO score-positive patients at first platinum-sensitive relapse in centres where complete resection can be achieved in most cases.
Niraparib is approved as first-line maintenance for all comers, making PARP inhibitor maintenance available beyond BRCA-mutated disease, though the benefit in proficient tumours is modest and long-term survival data are neutral.
Women with newly diagnosed advanced ovarian cancer should have their tumour tested for BRCA mutations and homologous recombination deficiency, because those who are HRD-positive gain years of additional disease control and better survival from adding olaparib to bevacizumab maintenance. Those who are HRD-negative gain nothing from olaparib in this combination and should not be exposed to its toxicity and cost. HRD testing has become a routine part of ovarian cancer care as a result.
Every woman diagnosed with advanced high-grade ovarian cancer should be tested for BRCA mutations at diagnosis, because those who carry one should receive two years of olaparib after chemotherapy, which greatly extends the time in remission and improves long-term survival. The plateau in the survival curves suggests some patients are cured by this approach. Toxicity is mostly anaemia, fatigue and nausea, and the two-year limit appears sufficient.
Query for this cancer: (TITLE:"Platinum-sensitive ovarian cancer" OR ABSTRACT:"Platinum-sensitive ovarian cancer" OR TITLE:"Platinum-sensitive relapsed ovarian cancer" OR ABSTRACT:"Platinum-sensitive relapsed ovarian cancer" OR TITLE:"Newly diagnosed ovarian cancer in response to platinum" OR ABSTRACT:"Newly diagnosed ovarian cancer in response to platinum" OR TITLE:"Platinum-free interval over six months" OR ABSTRACT:"Platinum-free interval over six months") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Platinum-sensitive ovarian cancer, not a curated reading list.
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Bleeding that does not stop by itself, bleeding from more than one site, or new bruising in several places or one large area.
A swollen painful calf, or sudden breathlessness with chest pain; venous thromboembolism including pulmonary embolism is a labelled warning.
Sudden severe abdominal pain, a hard or very tender abdomen, or abdominal pain with vomiting and fever. Boxed warning for gastrointestinal perforation on bevacizumab.
Not CYP-metabolised (carboxylesterases), so few pharmacokinetic interactions. Hypertension and tachycardia: monitor blood pressure weekly for 2 months.
Avoid grapefruit and Seville oranges.
Dose by Calvert formula using GFR (see the calculators).
See all on the product pages:BevacizumabCarboplatinGemcitabineNiraparibOlaparibPaclitaxel / nab-paclitaxelPegylated liposomal doxorubicinRucaparib·Printable cards in the navigator
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