Finding a cure for cancer is a quest that motivates many young physicians and researchers to choose the Oncology field. Later, during his or her career, confronted with the reality of cancer, very often an oncologist feels like a despondent samurai that has to keep on fighting against all odds, outnumbered by a ruthless and devious enemy. Every time a cancer clinical trial or a new drug is introduced by media as a “cancer cure”, I read the news with a mixture of hope and skepticism. Why skepticism? I distinctly remember two previous instances of “cancer cure” pep and hype sensationalist media announcements that made me believe for a moment that the unforeseen has happened.
First, after several exceptional responses to angiostatin in a lung cancer mouse model, James Watson declared for the May 3d, 1998 edition of The New York Times that “Judah Folkman will cure cancer in 2 years”. Unfortunately, the clinical trials using angiostatin in human lung cancer were not as successful and, the pharmaceutical company that Judah Folkman created, filed for bankruptcy. Few years later, the patents for angiostatin and endostatin, two angiogenesis inhibitors isolated by Folkman, were sold to China and, in 2018, Endostar (endostatin) was approved by China’s State Food and Drug Administration (CFDA) for the treatment of non-small cell lung cancer. Folkman’s brilliant idea to target angiogenesis was
subsequently picked-up by other pharmaceutical companies and, several years later, bevacizumab and other anti-angiogenic drugs were developed and demonstrated clinical benefit in several cancer types.
Second, three years later, in May 2001, the cover of Times Magazine announced the introduction of Gleevec in the treatment of chronic myeloid leukemia (CML) querying rhetorically whether Gleevec is “the breakthrough we’ve been waiting for”. Well, yes, yes, and no. Yes, because Gleevec gave patients with CML a chance for long-term survival and even cure. Yes, because Gleevec became the herald of the tyrosine kinase inhibitors (TKIs) era that introduced in the oncology armamentarium dozens of targeted small molecules. No, because with the exception of CML and few other instances, after a period of initial response, TKIs induce therapeutic resistance in most types of cancer. On June 5th, 2022 at the American Society of Oncology (ASCO) annual meeting, that took place in Chicago, a new “cancer cure” using dostarlimab, a PD-1 inhibitor was publicized. According to Dr. Andrea Cercek’s ASCO presentation, all of the first 14 locally advanced rectal cancer patients enrolled in a neo-adjuvant dostarlimab clinical trial responded and none of them recurred during follow-up (range, 6 to 25 months). These results, published simultaneously on June 5th in the New England Journal of Medicine are stunning. 100% of the 14 patients treated achieved complete remission that was maintained for at least one year in 50% of them. The resolution of symptoms was also very fast, occurring within 9 weeks of starting the treatment in 80% of the patients. A breakthrough? Of course. The toxicities associated with chemotherapy, radiotherapy or surgery were avoided in all the patients treated with dostarlimab. An important note though: all rectal tumors were mismatch-repair deficient, which made them particularly sensitive to immunotherapy. Another key point: only 5-10% of rectal cancers are mismatch-repair deficient and, therefore, this approach applies only to a minority of rectal cancer patients. In conclusion, at this time, it is premature to call dostarlimab the new standard of care treatment for locally advanced rectal cancer, as currently we do not know for how long these remarkable responses will be maintained.
Regardless, the results are outstanding, and, clearly, they represent a proof of principle and are a breakthrough. Administering the right drug, in the right amount, to the right patient, at the right time may cure some forms of cancers. Personalized/precision treatments work in selected patients. ASCO 2022? A lot of glitter and hype, but also some real hope.