PACIFIC-2
Started by gongdoli
Probably full. Looks like actual enrollment is greater than expected enrollment.
Concurrent immuno with RT has thus far been a loser (CALLAS, some H&N data), but let's see what it shows in the 2nd diagnosis where it made a splash.
If it's a positive trial it'll definitely get added in although I'd be wary of the toxicity of concurrent Durva with lung RT (which I'm sure they're monitoring closely).
If it's a positive trial it'll definitely get added in although I'd be wary of the toxicity of concurrent Durva with lung RT (which I'm sure they're monitoring closely).
Two points:
1. Pacific 2 does not ask if concurrent + adjuvant Durva is superior to adjuvant Durva. The control arm is no Durva, thus not current s.o.c. I have no idea, why it was designed that way.
It will likely come out positive, but will be difficult to interpret.
2. Phase II data for concurrent Nivolumab have been published.
Safety was ok, but efficacy was not „WOW“
Safety evaluation of nivolumab added concurrently to radiotherapy in a standard first line chemo-radiotherapy regimen in stage III non-small cell lung cancer-The ETOP NICOLAS trial - PubMed
As of 13 December 2018, 82 patients were recruited with median follow-up of 13.4 months. The most frequent adverse events (AEs) were anaemia, fatigue and pneumonitis. No unexpected AEs or increased toxicities were observed. For the first 21 patients, no grade-≥3-pneumonitis was observed by the...
pubmed.ncbi.nlm.nih.gov
Progression-Free and Overall Survival for Concurrent Nivolumab With Standard Concurrent Chemoradiotherapy in Locally Advanced Stage IIIA-B NSCLC: Results From the European Thoracic Oncology Platform NICOLAS Phase II Trial (European Thoracic Oncology
PFS and OS are arithmetically higher in studies involving the same population. However, on the basis of the formal hierarchical efficacy analysis, we could not reject that the 1-year PFS rate is at least 45%.
pubmed.ncbi.nlm.nih.gov
1. Womp womp. I'm sure there will be inappropriate cross trial comparisons to Pacific 1 experimental arm. They didn't submit a protocol amendment when PACIFIC-1 came out?Two points:
1. Pacific 2 does not ask if concurrent + adjuvant Durva is superior to adjuvant Durva. The control arm is no Durva, thus not current s.o.c. I have no idea, why it was designed that way.
It will likely come out positive, but will be difficult to interpret.
2. Phase II data for concurrent Nivolumab have been published.
Safety was ok, but efficacy was not „WOW“
Safety evaluation of nivolumab added concurrently to radiotherapy in a standard first line chemo-radiotherapy regimen in stage III non-small cell lung cancer-The ETOP NICOLAS trial - PubMed
As of 13 December 2018, 82 patients were recruited with median follow-up of 13.4 months. The most frequent adverse events (AEs) were anaemia, fatigue and pneumonitis. No unexpected AEs or increased toxicities were observed. For the first 21 patients, no grade-≥3-pneumonitis was observed by the...Progression-Free and Overall Survival for Concurrent Nivolumab With Standard Concurrent Chemoradiotherapy in Locally Advanced Stage IIIA-B NSCLC: Results From the European Thoracic Oncology Platform NICOLAS Phase II Trial (European Thoracic Oncology
PFS and OS are arithmetically higher in studies involving the same population. However, on the basis of the formal hierarchical efficacy analysis, we could not reject that the 1-year PFS rate is at least 45%.
2. Thanks for the links. If adding more therapies does not improve OS, we should not use them. If they improve PFS and not OS, we should critically discern if there is any advantage of using them in the adjuvant setting vs in the salvage setting. Common sense would say no.
Indeed. And no, they did not.
However, bear in mind that since IO runs parallel to CRT in Pacific-2, RT is part of trial treatment and patients enter the trial prior to CRT. Thus, it is likely that patients in Pacific-2 are better selected than those in the original Pacific trial and receive higher quality CRT.
Data from the original pacific study still pretty damn amazing
Of course they are. But also bear in mind that these patients also represent a positive selection.
Those are patients that completed CRT for stage III NSCLC, were not progressive and deemed fit enough start IO within weeks after completion of CRT.
Comparing patients from both trials is going to be tricky.
Also bear in mind that the crossover numbers from original pacific have not been published. We don’t know how many patients in control arm went on to receive IO at progression and the protocol was not amended to mandate this despite Keynote data establishing this as standard of care. And as mentioned above, it’s a well-selected, fit group; other data suggests the regimen is more toxic in practice than what was seen on the trial. Pacific is impressive and SOC but the data are not without question.
