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CONKO-003 was the first randomised trial to show a second-line chemotherapy helps in pancreatic cancer: adding oxaliplatin to fluorouracil after gemcitabine failed lengthened median survival from 3.3 to 5.9 months, which is why oxaliplatin-based second-line treatment is in the NICE guideline. A later Canadian trial with a different oxaliplatin schedule found the opposite.
CONKO-003 randomised 168 patients whose disease had progressed on gemcitabine monotherapy to OFF (oxaliplatin 85 mg/m2 on days 8 and 22 with folinic acid and 24-hour fluorouracil on days 1, 8, 15 and 22 of a 42-day cycle) or FF alone, stratified by metastases, duration of first-line therapy and Karnofsky status. With a median follow-up of 54.1 months, median overall survival was 5.9 months (95 percent confidence interval 4.1 to 7.4) with OFF against 3.3 months (2.7 to 4.0) with FF (hazard ratio 0.66, 0.48 to 0.91; p 0.010) and time to progression 2.9 against 2.0 months (hazard ratio 0.68); adverse events were similar apart from grade 1 to 2 neurotoxicity (38.2 against 7.1 percent). PANCREOX (108 Canadian patients, 2016) then found modified FOLFOX6 no better for progression-free survival and worse for overall survival than infusional fluorouracil and leucovorin (6.1 against 9.9 months; p 0.02) with grade 3 to 4 events in 63 against 11 percent, so the oxaliplatin schedule matters. NICE NG85 recommends oxaliplatin-based second-line chemotherapy for people who have not had first-line oxaliplatin (1.9.7) and gemcitabine-based treatment after first-line FOLFIRINOX (1.9.8); daraxonrasib (RASolute 302) now supersedes both where it is available.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
168 randomised.
95% CI 4.1 to 7.4; 160 patients in the primary analysis · 95% CI 2.7 to 4.0
Source| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Overall survivalprimary | OFF (oxaliplatin, folinic acid, fluorouracil) | - | 5.9 months | 0.66 (0.48 to 0.91) | 0.010 | link |
| FF (folinic acid, fluorouracil) | - | 3.3 months |
Shares Leucovorin (folinic acid), Oxaliplatin, Platinum agents, Metastatic pancreatic ductal adenocarcinoma.
Shares Leucovorin (folinic acid), FOLFOX (5-FU, leucovorin, oxaliplatin), Oxaliplatin, Fluorouracil (5-FU).
Shares Peripheral neuropathy (chemotherapy-induced), Leucovorin (folinic acid), Fluorouracil (5-FU), Metastatic pancreatic ductal adenocarcinoma.
Shares Leucovorin (folinic acid), FOLFOX (5-FU, leucovorin, oxaliplatin), Oxaliplatin, Fluorouracil (5-FU).
Shares Leucovorin (folinic acid), FOLFOX (5-FU, leucovorin, oxaliplatin), Oxaliplatin, Fluorouracil (5-FU).
Shares RASolute 302, Leucovorin (folinic acid), Fluorouracil (5-FU), Metastatic pancreatic ductal adenocarcinoma.
Shares Leucovorin (folinic acid), FOLFOX (5-FU, leucovorin, oxaliplatin), Oxaliplatin, Fluorouracil (5-FU).
Shares Leucovorin (folinic acid), Oxaliplatin, Fluorouracil (5-FU), Platinum agents.