5 ms·

Unprecedented 100% of First 14 Patients with Cancer Respond to Dostarlimab

76 points by zw123456 4y ago

mcbain 4y ago
Previous discussion when this result came out at ASCO: https://news.ycombinator.com/item?id=31630679 https://news.ycombinator.com/item?id=31630679
akira2501 4y ago
Is this medication produced using hybridomas? The idea of using a tumor to produce antibodies that fight other tumors is something that would have been hard to predict.
- asdff 4y ago
  It's produced with these: https://en.wikipedia.org/wiki/Chinese_hamster_ovary_cell https://en.wikipedia.org/wiki/Chinese_hamster_ovary_cell
asdff 4y ago
"Unprecedented" is a little bit unneeded considering this is a PD-1 immunotherapy used against a mismatch repair deficient cancer, these results are not surprising. See Le et al NEJM 2015.
- dmix 4y ago
  Referring to https://www.nejm.org/doi/full/10.1056/NEJMoa1500596 https://www.nejm.org/doi/full/10.1056/NEJMoa1500596 ? Reading a follow up study: > Kaplan-Meier estimates of the 5-year OS [overall survial] rate were 31.9% for the pembrolizumab group and 16.3% for the chemotherapy group. Thirty-nine patients received 35 cycles (ie, approximately 2 years) of pembrolizumab, 82.1% of whom were still alive at data cutoff (approximately 5 years). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280089/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280089/ That's a pretty good improvement
  - evandijk70 4y ago
    You are comparing the wrong numbers, 5 year-OS vs objective response. Objective response is 46% in the study you cited (Table 2). 5 year-OS is nearly always lower. The patients in the new study were only followed for a median of 6.8 months, and unfortunately, the odds are high that not all of them will survive that long.
londons_explore 4y ago
For cases like this, exponentially scaled studies should be allowed. Current practice is to enroll 14 participants (and some control participants) and wait many months for the results to roll in, which, if the treatment is effective lets people not on the treatment die unnecessarily. A better approach is to have a rolling approach. Ie. Every time a potential participant is found, they are allowed to join the study if the results from all other participants show that it is statistically beneficial, minus a risk budget. So if a treatment does really well like this, then it will quickly expand to a large number of participants. There is no need to wait for results - as soon as the current cohort of participants survives a few extra days, or as soon as someone in the control group dies, you can enroll a few more participants. And if a treatment is marginal, then the group size will only expand very slowly, or not at all, as more and more data is collected from existing participants. If the data starts to show a detrimental effect of the same size or larger than the risk budget, then the study can take on no new participants, and if the collected data is not enough to approve the treatment then the result is a failure.
- londons_explore 4y ago
  This also opens the door to eliminating stage 1/2/3 trials. Let the study leadership decide how to spread their risk budget, and to overlap them if they choose to.
  - refurb 4y ago
    They already do this, especially for cancer. Phase 3 trials aren't always needed. Phase I/IIb are common.
- lrem 4y ago
  I imagine the test protocols are heavily regulated. Getting what you describe right is within reach of experiment design... But updating regulations in a mathematically correct way is a whole new challenge. And given the current state of globalisation, an interested party would need to convince multiple government bodies, using multiple languages. Which means we'd need an interested party with deep pockets and good motivation.
Protostome 4y ago
Not sure if it means that the drug is more effective than other PD1/L1 inhibitors or pharma companies simply learned how to better select their clinical trial participants to optimize the outcomes ...

76 points by zw123456 4y ago

Previous discussion when this result came out at ASCO: https://news.ycombinator.com/item?id=31630679 https://news.ycombinator.com/item?id=31630679

akira2501 4y ago

Is this medication produced using hybridomas? The idea of using a tumor to produce antibodies that fight other tumors is something that would have been hard to predict.

asdff 4y ago
It's produced with these: https://en.wikipedia.org/wiki/Chinese_hamster_ovary_cell https://en.wikipedia.org/wiki/Chinese_hamster_ovary_cell

asdff 4y ago

"Unprecedented" is a little bit unneeded considering this is a PD-1 immunotherapy used against a mismatch repair deficient cancer, these results are not surprising. See Le et al NEJM 2015.

dmix 4y ago
Referring to https://www.nejm.org/doi/full/10.1056/NEJMoa1500596 https://www.nejm.org/doi/full/10.1056/NEJMoa1500596 ? Reading a follow up study: > Kaplan-Meier estimates of the 5-year OS [overall survial] rate were 31.9% for the pembrolizumab group and 16.3% for the chemotherapy group. Thirty-nine patients received 35 cycles (ie, approximately 2 years) of pembrolizumab, 82.1% of whom were still alive at data cutoff (approximately 5 years). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280089/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280089/ That's a pretty good improvement
- evandijk70 4y ago
  You are comparing the wrong numbers, 5 year-OS vs objective response. Objective response is 46% in the study you cited (Table 2). 5 year-OS is nearly always lower. The patients in the new study were only followed for a median of 6.8 months, and unfortunately, the odds are high that not all of them will survive that long.

londons_explore 4y ago

For cases like this, exponentially scaled studies should be allowed. Current practice is to enroll 14 participants (and some control participants) and wait many months for the results to roll in, which, if the treatment is effective lets people not on the treatment die unnecessarily. A better approach is to have a rolling approach. Ie. Every time a potential participant is found, they are allowed to join the study if the results from all other participants show that it is statistically beneficial, minus a risk budget. So if a treatment does really well like this, then it will quickly expand to a large number of participants. There is no need to wait for results - as soon as the current cohort of participants survives a few extra days, or as soon as someone in the control group dies, you can enroll a few more participants. And if a treatment is marginal, then the group size will only expand very slowly, or not at all, as more and more data is collected from existing participants. If the data starts to show a detrimental effect of the same size or larger than the risk budget, then the study can take on no new participants, and if the collected data is not enough to approve the treatment then the result is a failure.

londons_explore 4y ago
This also opens the door to eliminating stage 1/2/3 trials. Let the study leadership decide how to spread their risk budget, and to overlap them if they choose to.
- refurb 4y ago
  They already do this, especially for cancer. Phase 3 trials aren't always needed. Phase I/IIb are common.
lrem 4y ago
I imagine the test protocols are heavily regulated. Getting what you describe right is within reach of experiment design... But updating regulations in a mathematically correct way is a whole new challenge. And given the current state of globalisation, an interested party would need to convince multiple government bodies, using multiple languages. Which means we'd need an interested party with deep pockets and good motivation.

Protostome 4y ago

Not sure if it means that the drug is more effective than other PD1/L1 inhibitors or pharma companies simply learned how to better select their clinical trial participants to optimize the outcomes ...