New Cancer Treatment.
PD-1 blockade in mismatch, repair-deficient locally advanced rectal cancer.
100% of 36 patients with immune system-resistant cancer have responded to a new cancer treatment using a monoclonal antibody, without needing chemo or radiotherapy. This is great news. Basically, they are removing impediments to the body repairing itself.
Note the first study was published in June 2022, and this technique is now being used in treatments around the world1
PD-1 receptor
The PD-1 receptor (stands for Programmed Cell-Death Receptor) is a protein that signals immune cells not to attack the body’s own cells. Some cancers are particularly nasty, because the cancer cells have the PD-1 protein on the surface of the cancer cells, and so the immune system will not attack those cancer cells, meaning that the cancer can spread unhindered by the body’s own defenses. PD-1 is expressed across a broad range of tumour cells in cancers as diverse as breast, bone, liver, lung, kidney, oesophagus, ovary, pancreas, prostate, skin, intestinal, stomach, thyroid.
12 patients in the study, 4 more now on a course of dostarlimb
In the first study, 12 patients with mismatch repair-deficient, advanced colorectal cancer received 500mg of dostarlimb, a monoclonal antibody, intravenously every 3 weeks for six months, and no other therapy. It was decided at the start that if the patients didn’t respond they would be given chemo/radiotherapy afterwards, but not one of the patients needed it. It was also decided that a clinically significant response would be a success rate of 25% or more; the observed response rate to chemotherapy is 7% (8 of 115 patients). In other words, if someone with this cancer has chemo, it only has a 7% chance of helping.
100% success rate.
All of the patients responded to the monoclonal antibody, the majority of patients had no sign of a viable tumour as early as 6 weeks after therapy began. All are still without any sign of cancer 6-12 months after the therapy.
And the side effects were fairly minor (rash or dermatitis, pruritis, fatigue, nausea; one patient had thyroid function abnormalities.)
They conclude that a larger study is needed, to confirm the result, but it looks like great news for cancer sufferers.
Literature review: 148 patients have been helped so far.
Ultimately according to Pastorino et al’s literature review, over 148 patients have now responded to this treatment with a 100% success rate and no re-growth or relapses have recurred; none of the 112 patients with colon cancer (after 13 months) and 36 patients with colorectal cancer (after nine months) have relapsed so far.
The first study:
PD-1 Blockade in Mismatch Repair–Deficient, Locally Advanced Rectal Cancer, Andrea Cercek, Melissa Lumish, Jenna Sinopoli, Jill Weiss, Jinru Shia, Michelle Lamendola-Essel, Imane H. El Dika, Neil Segal, Marina Shcherba, Ryan Sugarman, Zsofia Stadler, Rona Yaeger, J. Joshua Smith, Benoit Rousseau, Guillem Argiles, Miteshkumar Patel, Avni Desai, Leonard B. Saltz, Maria Widmar, Krishna Iyer, Janie Zhang, Nicole Gianino, Christopher Crane, Paul B. Romesser, Emmanouil P. Pappou, Philip Paty, Julio Garcia-Aguilar, Mithat Gonen, Marc Gollub, Martin R. Weiser, Kurt A. Schalper, Luis A. Diaz New England Journal of Medicine, pp 2363 - 2376 v386 issue 25. Massachusetts Medical Society 0028-4793 doi: 10.1056/NEJMoa2201445 https://doi.org/10.1056/NEJMoa2201445 2024/04/04
Abstract
Sixteen patients with mismatch repair-deficient, locally advanced rectal cancer were enrolled in a pilot study in which 6 months of neoadjuvant anti-PD-1 therapy was to be followed by surgical resection. Twelve patients have completed treatment and have had at least 6 months of follow-up; all 12 had a clinical complete response. All imaging tests and biopsies have shown no viable tumor.
Results:
A total of 12 patients have completed treatment with dostarlimab and have undergone at least 6 months of follow-up. All 12 patients (100%; 95% confidence interval, 74 to 100) had a clinical complete response, with no evidence of tumor on magnetic resonance imaging, 18F-fluorodeoxyglucose–positron-emission tomography, endoscopic evaluation, digital rectal examination, or biopsy. At the time of this report, no patients had received chemoradiotherapy or undergone surgery, and no cases of progression or recurrence had been reported during follow-up (range, 6 to 25 months). No adverse events of grade 3 or higher have been reported.
Addendums
Epoch covered this story:
Other monoclonal antibodies have worked well also for colon cancer, and there is hope that this is a truly revolutionary therapy:
Alessandro Pastorino, Fabio Catalano, John R. Zalcberg, Alberto Sobrero, Cross-trial comparisons for the adjuvant treatment of MSI colorectal cancer: dare to dream the future scenarios., European Journal of Cancer, Volume 199, 2024, 113538, ISSN 0959-8049, https://www.sciencedirect.com/science/article/pii/S0959804924000145
Abstract: The remarkable outcomes achieved with neoadjuvant checkpoint inhibitors for patients diagnosed with MSI colorectal cancer hold the potential to revolutionize the treatment landscape in this context. Specifically, the combination of nivolumab plus ipilimumab in colon cancer and dostarlimab in rectal cancer has led to an unprecedented rate of complete pathological and clinical responses. Notably, these responses have been further substantiated by the absence of relapses, with a 0% relapse rate observed during the first year of follow-up. The significance of these achievements becomes even more apparent when compared to the relatively high relapse rates, ranging from 11% to 28%, observed in MSI colorectal cancer cases treated neoadjuvantly with chemo(radio)therapy. However, it is crucial to exercise caution when interpreting such exceptional responses in oncology, especially within a short follow-up period. The future implications of these findings will depend on how the data mature over time. In this manuscript, we attempt to explore the potential scenarios that may unfold in the near future.
Cercek et al are conducting a huge international trial of dostarlimab right now:
Andrea Cercek et al., Phase II, single-arm, open-label study of dostarlimab monotherapy in previously untreated patients with stage II/III dMMR/MSI-H locally advanced rectal cancer.. JCO 41, TPS3639-TPS3639(2023). DOI:10.1200/JCO.2023.41.16_suppl.TPS3639
These articles are from June 2022 when the first study was published:
https://www.mskcc.org/news/rectal-cancer-disappears-after-experimental-use-immunotherapy
Vigilant Fox covered this story, which is why I looked into it:
https://onlinelibrary.wiley.com/doi/10.5694/mja2.52218