New Delhi: Cancer is one of the leading causes of death worldwide. It accounted for about 10 million deaths in 2020. With advancements in medical science, scientists are working towards finding a cure and the best methods of treating cancer. The recent clinical trial conducted at Memorial Sloan Kettering Cancer Center (MSK) where patients were enrolled for a clinical trial in treating rectal cancer involving immunotherapy as created a buzz. As a group of 12 rectal cancer patients who underwent the trial showed no signs of a tumour after taking an antibody drug for six months, this ongoing medical trial in the US is now seen as a new beginning in the rectal cancer space.
The MSK clinical trial was investigating for the first time ever if immunotherapy alone could beat rectal cancer that had not spread to other tissues, in a subset of patients whose tumours contain a specific genetic mutation.
In every case, rectal cancer disappeared after immunotherapy without the need for the standard treatments of radiation, surgery, or chemotherapy and cancer has not returned in any of the patients, who have been cancer-free for up to two years.
What is rectal cancer?
Rectal cancer is a tumour that arises from the lowermost part of the digestive tract, just proximal to the anal canal. It usually spreads to the lymph nodes that line it, in which case it is called a locally advanced cancer, prior to its spread to other distant organs, when it is deemed a metastatic/ advanced disease.
Rectal cancer is usually detected in advanced stages as it is generally ignored by many thinking that it is piles. The standard of treatment for locally advanced disease is concurrent chemotherapy and radiation followed by surgery and sequential chemotherapy. The treatments can be in isolation or in conjunction. Treatments can have significant side effects.
Tesaro’s work on Dostarlimab
Tesaro, a biotech company based out of Massachusetts developed the drug. Tesaro was acquired by GlaxoSmithKline in 2019, dostarlimab is also known by the brand name Jemparli. Dostarlimab was developed to treat women with recurrent or advanced endometrial cancer.
On August 17, 2021, the FDA approved dostarlimab-gxly (brand name Jemperli) for adult patients with mismatch repair-deficient recurrent or advanced solid tumours, as determined by an FDA-approved test, that have progressed on or following prior treatment and who have no satisfactory alternative treatment options.
Rectal cancer remission
According to reports, 18 patients in the clinical trial took Dostarlimab for around six months and after over 12 months the doctors found that their cancer disappeared. While it’s a small trial so far, the results have been impressive; they were published in The New England Journal of Medicine and featured at the nation’s largest gathering of clinical oncologists in June 2022.
In every case, rectal cancer disappeared after immunotherapy — without the need for the standard treatments of radiation, surgery, or chemotherapy — and cancer has not returned in any of the patients, who have been cancer-free for up to two years.
It’s incredibly rewarding to get these happy tears and happy emails from the patients in this study who finish treatment and realise, ‘Oh my God, I get to keep all my normal body functions that I feared I might lose to radiation or surgery,’ expressed Dr Andrea Cercek, Medical Oncologist, Memorial Sloan Kettering Cancer Center (MSK).
Dr Cercek added, “The most exciting part of this is that every single one of our patients has only needed immunotherapy. We haven’t radiated anybody, and we haven’t put anybody through surgery.” She continued, “They have preserved normal bowel function, bladder function, sexual function, fertility. Women have their uterus and ovaries. It’s remarkable.”
This clinical trial could pave the way for treating other forms of cancer in the future. As the trial continues at MSK, Dr Luis Alberto Diaz, Medical Oncologist, Memorial Sloan Kettering Cancer Center (MSK) said, “It’s the tip of the iceberg.” He explains, “We are investigating if this same method may help other cancers where the treatments are often life-altering and tumours can be MMRd. We are currently enrolling patients with gastric (stomach), prostate, and pancreatic cancers.”
Dostarlimab clinical trial reception by the Indian medical community
Since the trial results have been published, it has created a lot of buzz and has got the entire medical community discussing how it could pave the path for future treatment for various cancers, ETHealthWorld spoke to few experts on the drug trial.
Commenting on the trial, “It is definitely a big step towards efficient cancer care. The preliminary data on Dostarlimab PD1 monotherapy has been very encouraging in high-risk rectal cancer patients and has been recently presented at the ASCO meeting in Chicago and subsequently published in NEJM. We would definitely need further studies on larger groups of patients across the globe to establish it as a standard of care for rectal cancer. Trials are also being conducted to study its effectiveness for cervical cancer, and endometrial cancer amongst others,” said Dr Pankaj Kumar Panda, Senior Research Officer, Apollo Proton Cancer Centre.
This remission of cancer in all patients enrolled in the trial could pave the path for treating all types of cancer in the future. Dr PK Julka, Senior Director- Medical Oncology, Max Hospital, Lajpat Nagar said It is a major breakthrough study. This is a small phase II trial where we have found that only in mismatch repair-deficient cases where MSI is high and where there are deficient genes which do mismatch repair so these genes are deficient only in those cases Dostarlimab which is a PD1 inhibitor that works wonders. This is a six-month study of 18 patients. They have found good response, we hope the study continues for one year or two years, hope they find the same result.”
“Advancing knowledge and clinical research are bringing new treatments and hope. Immunotherapy seems to be promising. The small group of 18 patients who took Dostarlimab for around six months had their tumour disappear. These tumours had a specific genetic makeup known as mismatch repair-deficient (MMRd) or microsatellite instability (MSI). Immunotherapy unmasks the protection of the cancer cells thereby getting them killed. A milestone – for sure,” stated Prof (Dr) Narasimhaiah Srinivasaiah, Senior Consultant – Colorectal Oncology, Apollo Cancer Center, Bengaluru.
Dostarlimab could possibly be a major breakthrough in mankind’s war against cancer but the clinical trial needs to be expanded to other demographics and geographies. “The study that is being talked about a lot in the media is a very small study that involves 12 patients of rectal cancer. The results are very interesting where all the patients have responded completely to the course of Dostarlimab. These are very initial results and cannot be taken as a stand of care at present. We need to wait for further studies before we reach a conclusion. Many medicines which have shown results in test conditions have failed to show effectiveness in the clinical scenarios. Unless large studies are conducted by administering Dostarlimab to multiple patients we cannot take these results as definitive. We need what is called a randomised control trial to prove the effectiveness in a larger population,” remarked Dr Sandeep Nayak P, Director – Department of Surgical Oncology & Robotic & Laparoscopic Surgery, Fortis Hospitals, Bannerghatta Road, Bengaluru.
“The most recent data published from Memorial Sloan Kettering Cancer Center, on the immunotherapy drug, Dostarlimab, shows the most promising outcome for this stage of cancer, with all of the 12 study patients in complete remission or free of disease, 12 months post-treatment. They managed to remain cancer-free without the standard of care, as mentioned earlier. This is very exciting news given that they avoided the standard treatment and the attendant side effects, along with the good quality of life. We, however, would need longer follow up of these patients and more data on a larger population, before celebrating it as a substitute for the standard treatment. Remember, not all patients would benefit from this drug, as just 5-10 per cent (MSI-H subset) would be eligible for the drug. What should be celebrated however is the promise it holds, and who wouldn’t want all patients cured,” shared Dr Suparna Ajit Rao, Consultant – Medical Oncology, PD Hinduja Hospital & Medical Research Centre, Mahim, Mumbai.
The drug and the clinical trial hold a lot of praise in the treatment of cancer but the study needs to expand and the study needs to be conducted for a year or two to see if the results are the same or not.
Dr Diaz has coined a term for this new method of using immunotherapy alone to target MMRd tumours, calling it “immunoablative” therapy — that means using “immunotherapy to replace surgery, chemotherapy, and radiation to remove cancer.” Dr Diaz says, “That might sound futuristic — but in this trial, we have a clinical example where that happened.”
Dr Diaz is hopeful that this trial could pave the path for future cancer treatment and it is just the tip of the iceberg in treating various forms of cancer.