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RESEARCH SNAPSHOT
Dostarlimab provides complete clearance of advanced rectal cancer
A Phase II study has observed a complete clinical response in a small number of patients with advanced rectal cancer after 6 months of treatment with dostarlimab .
The possibility of a cure for advanced rectal cancer has been raised by the preliminary findings of a Phase II trial . The standard therapy for locally advanced rectal cancer is a combination of neoadjuvant induction chemotherapy , followed by chemoradiotherapy and then surgery . 1 Although patients with rectal cancer often require surgery , if neoadjuvant therapy is successful and provides a clinical complete response , it might be possible to avoid surgery . 2 Nevertheless , a problem for rectal cancer therapy is that between 5 % and 10 % of rectal adenocarcinomas are mismatch-repair deficient ; that is , the cells have mutations which impair their ability to correct mistakes in DNA during replication . As a result , such tumours respond poorly to standard neoadjuvant chemotherapy regimens . However , studies have shown that the use of immune checkpoint blockade ( programmed death 1 ( PD-1 ) blockade ) leads to enhanced treatment response in patients with mismatch repair-deficient tumours . 3
For this study , 4 researchers hypothesised that use of a PD-1 inhibitor in patients with locally advanced rectal cancer and with a mismatch repair-deficient tumour might be beneficial . The researchers undertook a prospective , Phase II study and enrolled patients with mismatch repair-deficient stage II or III rectal adenocarcinoma . Treatment consisted of the use of a single agent , dostarlimab at a dose of 500mg every 3 weeks for a total of 6 months , and which was followed by standard radiation therapy and surgery . However , the design was such that if
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patients achieved a complete clinical response after dostarlimab , then radiotherapy and surgery could be avoided . The researchers set the primary endpoint as a sustained clinical complete response 12 months after treatment with dostarlimab .
A total of 16 patients with a median age of 54 years ( 62 % female ) were enrolled in the trial , of whom 12 had been in the study for over 6 months ( a median follow-up time of 12 months ) and completed therapy with dostarlimab . Among the 16 patients , 15 had stage III disease and the most common presenting symptoms were rectal bleeding ( 88 %) of patients , constipation ( 31 %) and abdominal pain ( 25 %).
To date , all 12 patients have achieved a clinical complete response , none of whom have received radiotherapy or surgical resection . Patients were found to respond rapidly to treatment with dostarlimab , with a resolution of symptoms occurring within 9 weeks of initiating treatment for 81 % of the cohort .
Although this was a small study , the authors concluded that mismatch repairdeficient , locally advanced , rectal cancer appeared to be highly sensitive to dostarlimab although acknowledged that longer follow-up is required to assess the duration of their treatment response .
References 1 Cercek A et al . Neoadjuvant chemotherapy first , followed by chemoradiation and then surgery , in the management of locally advanced rectal cancer . J Nat Compr Canc Netw 2014 ; 12 ( 4 ): 513 – 19 . 2 Smith JJ et al . Assessment of a Watch-and-Wait Strategy for Rectal Cancer in Patients with a Complete Response After Neoadjuvant Therapy . JAMA Oncol 2019 ; 5 ( 4 ): e185896 . 3 Le DT et al . PD-1 Blockade in Tumors with Mismatch-Repair Deficiency . N Engl J Med 2015 ; 372 ( 26 ): 2509 – 20 . 4 Cercek A et al . PD-1 Blockade in Mismatch Repair- Deficient , Locally Advanced Rectal Cancer . N Engl J Med 2022 ; 386 ( 25 ): 2363 – 76 .
Hospitalisation risk from COVID is lower for infants of fully vaccinated mothers
Although pregnant women were excluded from the efficacy trials of the currently approved COVID-19 vaccines , the subsequently collected data suggested that they are safe in pregnant women . 1 In fact , evidence indicates that there was a 61 % reduced risk of hospitalisation for COVID-19 among infants less than 6 months old if their mothers had received two doses of a COVID-19 vaccine . 2 However , these data were collected during the period when the Delta variant was the main circulating agent and much less is known about the impact of maternal vaccination when Omicron was the main circulating variant .
For the present study , 3 US researchers
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