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Recently, for the first time in medical history, a small group of rectal cancer patients in a clinical trial conducted by Memorial Sloan Kettering Cancer Center, Manhattan, New York, experienced a miraculous escape from the disease during the entire trial by using Dostarlimab that was given to a group of 12 colorectal cancer patients for six months. All of them recovered fully.
The medical trial was funded by the Simon and Eve Colin Foundation, GlaxoSmithKline, Stand Up to Cancer, Swim Across America and the National Cancer Institute of the National Institutes of Health.
This clinical trial was published by a team of 32 researchers recently, in one of the most prestigious medical journals “New England Journal of Medicine”.
Since none of the participants in this experiment reported any major serious side effects, the results of this clinical research are causing a stir in the medical profession, social media, and media outlets.
Says Dr Sewanti Limaye, Director, Precision and Medical Oncology at Sir HN Reliance Foundation Hospital “I feel that this trial that was published in the New Journal of medicine for rectal cancer patients sends out two strong messages across the world. In this trial, early-stage rectal cancer patients responded 100 per cent to the immunotherapy drugs that were offered to them. But it was offered to them as a part of clinical trial because they tested positive for a particular genetic alteration called MSI high”.
There were 18 patients who had 100 per cent response but the tumour was tested for this particular biomarker called MSI high. MSI high tacker was on one of the eligibility for the trial. Since they had 100 per cent response, they could negate or escape and did not require surgery, radiation and chemotherapy that is how normally rectal cancer is treated. Rectal cancer is treated with multimodality treatment.
First, they're given chemotherapy and radiation first then cool off post that surgery. Then chemotherapy for six months. One of the styles of the treatment for early stages of rectal cancer. But here those patients were found to be MSI high with only five per cent of rectal cancer genuine enough, these patients were then exposed to this particular immunotherapy or the drug that led to 100 per cent response.
Two important messages that came out from this finding. One is that the testing the patient to figure out the biomarker or the signature cancer which is very critical. Precision medicine is figuring out the biomarker in that particular patient's tumour and treating it based on the genomic signature. That's how you personalize the treatment for every patient. This story is a poster child of this concept because they detected the tumour in an early stage and took them to clinical trials and gave them drugs.
More than a decade ago it was found to be a biomarker for magical response to immunotherapy in advanced rectal cancer patients. Wall Street Journal had done a feature on this when it turned around the life of a dying young woman in the US. It was a breakthrough of Approval of immunotherapy for MSI high patients with advanced cancer. Now in this particular trial they moved the field upwards and gave immunotherapy to those patients who had MSI high genomic signature at an early stage and they were able to 100 per cent respond to it. So, the message is that do the genomic analysis and understand the biology of cancer and help figure the specific treatment of your specific problem. Precision is the way forward.
The second message is novel drugs in oncology were made first available for clinical trials. So, we have to be open to what options are and whether we're a candidate for them. Not everyone is a candidate for clinical trials and the oncologist of that patient may well understand that and be able to guide them. One needs to have an open mindset because by the time the drug is mature enough to be launched in the regular market. Not every novel drug will have such remarkable results but here there was a marriage of two things. One - very precise testing and second- a drug that worked well. This concept goes across borders and across countries and is globally applicable, he concluded.
Says Dr Arvind Badiger, technical director at BDR Pharmaceuticals, “Definitely, the news that has been published by the researchers seems quite promising about Dostarlimab, but however for now, I can’t make such a strong comment that it can be a game changer. But, off course the drug has been very-very effective as of now”.
“In India we are not doing any trials because the drug was approved by FDA for endometrial cancer, but study that is been published and promising results are seen for rectal cancer. We are not conducting any trials in India because the medicine has been approved by the FDA for endometrial cancer, but research has been published with promising results for rectal cancer. But, most crucially, the method by which both drugs act is the same. There is conventional therapy for rectal cancer, which includes chemotherapy drugs such as Capecitabine and Oxaliplatin, with known side effects. There are few anti-bodies like cetuximab and panitumumab to treat such diseases. Every cell in the human body has a shelf life, and cancerous cells are no exception. In many places where immunity is high, cancer cells die through a process known as programmed cell death. In many areas where immunity is high, cancer cells die through a process known as programmed cell death”, he said.
Program cell death is generally blocked in the rectal cancer cells where cancer has undergone stage metastasis. So, in such patients, the program is blocked because of this metastasis. This drug works as immunotherapy because of its nature of action and reverses this particular blocked program cell death. The trial that has been recently conducted has seen 100 per cent success by the clinicians.
A bold statement
According to Dr Prasad Kasbekar, Consultant Surgical Oncologist, Masina Hospital, Byculla, Mumbai, the article makes a very bold statement, especially for a cancer which is notorious for recurrence and relapse. The study showed a complete response in 12 patients treated and observed over a period of six months and after a panel of 32 specialists intensely scrutinized the treatment and patients, they concluded that the patients had a complete remission.
“We must understand that a complete remission is different from a cure in that the cancer has disappeared completely, but the patient has not been totally cured. Complete remission is rare in colon cancers so in that format the drug is definitely a very effective find”, he said.
“My criticisms to the trial are that 12 patients would also be too small a sample size to effectively deduce the effectiveness of the drug. However, Dostarlimab does definitely have promise in the treatment of colorectal cancers. Good response to medical therapy usually means better outcomes, whether it is chemotherapy, hormonal therapy or immunotherapy. Put in the factor of the potential to avoid a debilitating surgery, then this drug could work wonders. Putting all the above into perspective is also the cost factor, I expect the prices of the drug to be extremely high, thus affordability is also something one can consider, especially in a country of middle to lower income such as India”, he pointed out.
So, this study is definitely something to take note of, but will it replace surgery or radiation? Only time will tell. As per my estimate, this drug will definitely play an adjunctive role to the above treatments, as long-term effects and outcomes are still to be determined. We can only wait and monitor. Also, we are looking at longish time spans for Indian patients as the drug still needs a formal introduction into the market, receive all clearances and is finally exported to India and other countries in the world, Dr Prasad Kasbekar said.
Currently, colorectal malignancies are treated with a combination of immunotherapy, chemotherapy, surgery, and radiation treatment. These treatments can be used alone or in conjunction with one another. These therapeutic regimens have been linked to side effects and significant consequences such as infertility, gastro-intestinal issues, urinary difficulties, and treatment-refractory illness, according to studies.
As a result of the effective medical treatment of rectal cancer with Dostarlimab, it is emphasized that therapeutic research trials across India, including Jammu and Kashmir, be initiated. The US Food and Drug Administration (FDA) gave expedited clearance to this drug on August 17, 2021, for the treatment of solid tumours for which there were no suitable alternative treatment choices.
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