Metastatic Anal Cancer: Weighing a Fourteen-Percent Response Rate Against the Alternative
An accelerated approval built on a single-arm trial and a response rate under one in five forces an honest conversation about what that number actually buys, compared to the option it's meant to replace.
B.L., a 57-year-old man, has worked as a hospice chaplain for over a decade, work he describes as having taught him more about honest conversations than any training ever did — a perspective he's brought directly into his own treatment decisions since being diagnosed with metastatic anal squamous cell carcinoma eight months ago. He responded well to first-line carboplatin and paclitaxel, with a partial response lasting five months, but this week's scan confirmed unambiguous progression in liver and nodal disease. He is HIV-positive, on stable antiretroviral therapy for over fifteen years with an undetectable viral load and a CD4 count in the normal range — well-controlled disease that no longer represents the exclusion it once did from most modern trials.
Retifanlimab received accelerated approval for metastatic or recurrent squamous cell anal carcinoma progressing after platinum-based chemotherapy, based on a single-arm trial with an objective response rate of roughly fourteen percent — real, and durable when it occurs, but a number that means roughly six in seven patients will not see their disease shrink on the drug. There is no randomized trial comparing it directly against further cytotoxic therapy in this setting, and second-line chemotherapy options — single-agent taxanes among them — have their own modest, similarly single-arm-derived response rates without a clean head-to-head comparison either. B.L.'s own question, asked directly in this visit rather than left implicit, is whether a fourteen percent chance of a durable response is worth the infusion visits, monitoring, and immune-related toxicity risk compared with a chemotherapy option whose numbers are not clearly better, just more familiar. He has spent years helping other families sit with exactly this kind of uncertain arithmetic at the bedside, and says he'd rather be given the real numbers, however unsatisfying, than a confident-sounding recommendation dressed up to hide how little separates the two options.
Clinic visit after confirmed progression
I'd lean toward retifanlimab. The response rate in POD1UM-202 was around fourteen percent, and I want to be honest about that number rather than oversell it — but the responses that do occur tend to be durable, and immunotherapy's overall toxicity profile is often more manageable than another line of cytotoxic chemotherapy for a patient who's already been through one regimen.
I don't think the data actually support calling that a clear preference. There's no randomized trial putting retifanlimab head-to-head against second-line chemotherapy in this disease — both response rates come from single-arm or otherwise non-comparative data, and neither has been shown to be meaningfully better than the other. Calling one "the better choice" implies a level of confidence the evidence doesn't actually have.
I'm not saying immunotherapy is the wrong choice — I'm saying calling it the right one, on the numbers alone, overstates what fourteen percent from an uncontrolled trial actually tells us relative to the alternative.
Given that neither of you can honestly say one option is clearly better, I think this decision belongs to B.L. directly, with both numbers stated exactly as plainly as you've just stated them to each other. He has told us explicitly that he values clear information over being steered toward whichever option sounds more like "doing everything." I'd give him precisely what you two just gave each other, and let him choose.
Agreed, after both options were presented to B.L. with their actual response rates and evidence quality stated explicitly: he chose retifanlimab, understanding clearly that roughly six in seven patients do not respond, and that this reflects genuine clinical equipoise rather than a confidently superior choice.
The clinical pharmacologist's point — that neither regimen has data strong enough to justify a confident recommendation either way — was recorded as the operative framing for this decision, not resolved in favor of either option on efficacy grounds. Docetaxel remains the explicit next step if imaging at eight weeks shows no response.