NCI9673
NCI9673 was the first completed immunotherapy trial in anal cancer: nivolumab on its own shrank tumours in a quarter of heavily treated patients, which made PD-1 blockade a standard later option, but the follow-on randomisation showed that adding ipilimumab did not help and added toxicity.
Overview
NCI9673 was a multi-institutional phase 2 trial of the NCI Experimental Therapeutics Clinical Trials Network. Part A gave nivolumab to 37 patients with previously treated metastatic anal squamous cell carcinoma; part B randomised further patients to nivolumab alone or nivolumab with ipilimumab, with progression-free survival as the primary endpoint.
In part A nine of 37 patients responded (24 percent), including two complete responses, with few grade 3 events and no serious adverse events, which established PD-1 blockade as an option after chemotherapy. In part B median progression-free survival was 2.9 months with nivolumab and 3.7 months with the combination (hazard ratio 0.86, p 0.25), response rates were similar (17.4 against 21.5 percent), and grade 3 or worse treatment-related adverse events doubled with ipilimumab (25 against 12 percent). The corpus's metastatic anal cancer page cites NCI9673 for nivolumab after chemotherapy.
- 24 out of 100 people had their tumour shrink with Nivolumab.
- There was no comparison group, so this number cannot tell you how much of the effect is due to the treatment.
- A response rate counts how many people had their tumours shrink by a set amount; shrinking is encouraging but does not by itself show that people live longer or feel better.
- Median 3.7 vs 2.9 months with Nivolumab + ipilimumab compared with Nivolumab; about 0.8 months longer for half the group.
- A median is a midpoint: half the people did better than this and half did worse, so it is not a prediction for any one person.
- Put another way, the treated group had about 14 percent lower chance of the event at any given time (hazard ratio 0.86, likely range 0.6 to 1.23).
- The likely range for the hazard ratio crosses 1, so the difference could be due to chance.
- This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
- 21.5 vs 17.4 out of 100 had their tumour shrink with Nivolumab + ipilimumab compared with Nivolumab; 4.1 more per 100.
- Roughly one extra person helped for every 24 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.
- The p-value (0.89) means the difference could plausibly be due to chance.
- A response rate counts how many people had their tumours shrink by a set amount; shrinking is encouraging but does not by itself show that people live longer or feel better.
- Median 20 vs 15.9 months with Nivolumab + ipilimumab compared with Nivolumab; about 4.1 months longer for half the group.
- A median is a midpoint: half the people did better than this and half did worse, so it is not a prediction for any one person.
- Put another way, the treated group had about 2 percent lower chance of the event at any given time (hazard ratio 0.98).
- Overall survival counts deaths from any cause, so it is the most direct measure of whether a treatment helps people live longer.
- 25 vs 12 out of 100 reached this endpoint with Nivolumab + ipilimumab compared with Nivolumab; 13 more per 100.
- On this measure the first group did worse, not better.
- This endpoint is not one of the standard survival or response measures; read it alongside the trial's primary result.
- These results apply to the people the trial enrolled: Refractory metastatic squamous cell carcinoma of the anal canal after prior chemotherapy: single-arm nivolumab (part A), then a randomised comparison of nivolumab with or without ipilimumab (part B). People in a different situation may not see the same effect.
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.
143 enrolled.
95% CI 15 to 33; 2 complete and 7 partial responses
Source90% CI 2.0 to 5.6 · 90% CI 1.9 to 3.8
Source12 patients · 6 patients
Source| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Objective response rate, part Aprimary | Nivolumab | 37 | 24% | - | - | link |
| Progression-free survival, part Bprimary | Nivolumab + ipilimumab | - | 3.7 months | 0.86 (0.6 to 1.23) | 0.25 | link |
| Nivolumab | - | 2.9 months | ||||
| Objective response rate, part B | Nivolumab + ipilimumab | - | 21.5% | - | 0.89 | link |
| Nivolumab | - | 17.4% | ||||
| Overall survival, part B | Nivolumab + ipilimumab | - | 20 months | 0.98 | - | link |
| Nivolumab | - | 15.9 months | ||||
| Grade 3 or worse treatment-related adverse events, part B | Nivolumab + ipilimumab | - | 25% | - | - | link |
| Nivolumab | - | 12% |
Single-agent PD-1 blockade remains the immunotherapy standard after chemotherapy in metastatic anal cancer; CTLA-4 blockade adds toxicity without benefit.
PD-1 blockade is an option for metastatic anal cancer after chemotherapy, and the basis for later immunotherapy combinations in the disease.
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