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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
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.
| Setting | Approach | Guideline |
|---|---|---|
| First-line maintenance, BRCA-mutant | Olaparib for two years (SOLO-1), or olaparib with bevacizumab (PAOLA-1); niraparib as an alternative. | not mapped |
| First-line maintenance, HRD-positive BRCA-wild-type | Olaparib plus bevacizumab (PAOLA-1) or niraparib (PRIMA) after HRD testing. | not mapped |
| First-line maintenance, HRD-negative | Niraparib (PRIMA, smaller benefit) or bevacizumab; observation is reasonable after discussion. | not mapped |
| First platinum-sensitive relapse | 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. | not mapped |
| Relapse after PARP inhibitor | Platinum doublet; PARP rechallenge has limited benefit; trials of ATR, WEE1 and next-generation PARP1-selective inhibitors. | not mapped |