Cancer research in the news, for better and for worse

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Last year, I wrote about the crisis in Alzheimer’s research: a cruel affair involving a research direction and course of treatment built in part on papers with doctored data, and the heated venture-capitalist backstory that complicated the virtuosity of whistle-blowers. More recently, authors attempted to defend the original data, but the defenses were often just as damning. The scientific field remains shrouded in complex institutional and profit-driven politics.

But it’s not alone. We live in complicated times for establishing reliable authority claims, with even major scientific institutions enmeshed in for-profit (or further-university-funding) considerations. Although the COVID-19 pandemic could have been a time for more globalized thinking about empirical research, we were also treated to the most puerile corporate stories of a race between different companies gunning to strike rich on having the first, best vaccine on the market. Nationalist priorities also often favored keeping “home court advantage” for their own businesses, rather than engaging in more open-source international collaboration on scientific findings, and allowing other countries to develop urgently needed on-site vaccines.

Which is not to say that no strides were made: The COVID-19 pandemic vastly accelerated the development of more research facilities around the world, and invited a return to research pathways (like mRNA-based treatments) that have accelerated medical advances in a wide range of other vital realms. But while the scientific method is robust, its actors are human, and constrained in their work by whatever sociopolitical systems they occupy.

So too are those who report for a living, which can be a serious problem for the cultivation of greater media and scientific literacy, to improve overall civic life.

How can we become more proactive, media-conscious, and empirically driven respondents to science news? Three recent cancer advances offer a sense of the problem, and possible solutions:

A vaccine against pancreatic cancer recurrence?

On May 10, Nature reported the results of a Phase-I trial that used individualized vaccines crafted from T-cell neoantigens mutated by the body’s fight against pancreatic ductal adenocarcinoma, a disease with an 88 percent five-year mortality rate (at the most optimistic). This vaccine, autogene acevumeran, included up to 20 neoantigens per patient, and was used in a protocol that started with atezolizumab (another form of immunotherapy), and ended a four-drug chemotherapy regimen called mFOLFIRINOX.

Fifteen of sixteen study patients underwent the full protocol, and eight produced T-cells capable of targeting at least one neoantigen, with four producing T-cells targeting more than one. After 18 months, patients with T-cells that had at least learned to target one neoantigen had a longer median for recurrence-free survival (a delicate term, which the study stresses is not yet assured) compared to patients whose T-cells had not responded to treatment.

But it’s easier just to say we’ve found a vaccine for pancreatic cancer, right?

Which is precisely what most news sites have since done.

Expanded, Phase II trials are set to begin this summer. Researchers are keen to explore the utility of this treatment for other high-mortality cancers, too.

Lung cancer pill improves survival by 50 percent?

At the annual conference for the American Society of Clinical Society (ASCO), Roy S. Herbst presented findings published in April. Lung cancer is the cause of more cancer deaths globally than any other. His team had tested the use of Osimertinib in a Phase-III trial of 682 patients with later-stage non-small-cell lung cancer that presented with a mutated form of a cell growth gene and the protein it produces.

In these cancer cases, a complete surgical resection of the damaged lung tissue is standard treatment, followed by an “adjuvant” (secondary) protocol of chemotherapy if necessary. The adjuvant treatment being studied began after surgery and chemotherapy, in the form a daily pill.

The four-year disease-free survival (DFS) rate, over a placebo, was 70 percent for those on Osimertinib, versus 29 percent for those on the placebo. In the general population, the DFS was 73 on the pill, 38 without it.

These are wonderfully promising results from a late-stage study.

They also didn’t emerge out of the ether.

In 2016, C E McCoach and A Jimeno published on Osimertinib, which even prior to formal testing had been implemented for patients struggling with treatments for the mutation often found in non-small-cell lung cancer. The reason Herbst was able to compare his trial results with a general population is that the pill had already been in active clinical use, approved by the FDA, EU, and Japan after having “demonstrated a high objective response rate and progression-free survival in patients”.

Does this devalue recent reports on this “wonder drug”? Not exactly. But a better framing would have been that a recent drug trial confirms pre-existing clinical data: not that we had made a sudden new breakthrough with this research.

There are no easy answers as to how we’ll now strive to cultivate better. But we can start with ourselves, and our immediate communities. We can improve the care we give to stories offering sensationalist depictions of scientific advances.

Blood cancer progression cut 74 percent by modified T-cells?

Also presented at ASCO’s conference was data on a Phase-3, randomized, open-label drug trial published today, June 5, in The New England Journal of Medicine.

Multiple myeloma is considered an incurable cancer that affects plasma cells, a type of white blood cell found in bone marrow. The previous standard treatment was lenalidomide, but many patients do not respond to the drug. Trial patients had already gone through such options with no promising results. They then underwent a form of CAR T-cell therapy, a multi-process cancer treatment that draws from transplant, immune, and gene therapy. In this case, healthy T-cells were separated from the patient’s blood to construct ciltacabtagene autoleucel (“cilta-cel”), synthetic T-cells that can recognize and target certain cancer cells when reintroduced.

Although most reporting touts a 74 percent reduction, the formal paper states that in their trial group of 419 patients, “progression-free survival at 12 months was 75.9 percent [] in the cilta-cel group and 48.6 percent [] in the standard care group.” (Presumably a small number had marginal progression, to bring down that overall statistic for reduced cancer growth across the board.)

These are good findings, but there is a bigger story overlooked in extolling the survival and reduced progression rate for this form of blood cancer.

The other objective of this trial was to test the safety of cilta-cel itself. Johnson & Johnson supports this drug research under the brand name CARVYKTI, and its write-up on the promising news of cilta-cel reducing disease progression highlights the known side effects under scrutiny, too. These include Parkinson’s-like symptoms, Guillain-Barré Syndrome, Immune Effector Cell-Associated Neurotoxicity Syndrome, and Cytokin Release Syndrome. The hope with this research was that it would yield a higher safety rating for this drug, to invite its use for patients less advanced in their disease, and for similar CAR T-cell therapies for other cancers, too.

In this regard, the study was a “success” inasmuch as it did not indicate any new grave concerns for the drug.

However, in today’s posted medical paper, researchers reported that “most patients reported grade 3 or 4 adverse events during treatment”. Grade 3 events are “severe and undesirable adverse events” and grade 4 events are “life threatening or disabling adverse events”. Grade 5 events are fatal. The fact that grade 5 events did not manifest in these trials is a great win for the patients, researchers, and Johnson & Johnson. Nevertheless, care needs to be taken when reporting on the drug’s efficacy without addressing what its safety profile might mean for future CAR T-cell therapy in other cancers. Risking grades 3 and 4 side-effects might be a no-brainer for patients who have not responded well to other treatments, but time will tell if this is a “wonder drug” for other stages of this and other diseases, too.

Science reporting and us

I never mean to be a downer when I push back on poor science journalism, but this is a humanist issue. That aforementioned faulty Alzheimer’s research meant families suffered and lost life savings for years, due in large part to oversold promises of their loved ones receiving the best possible medication.

There is also something crushing about the positively spun story of how COVID finally shone a light on mRNA research that had been sidelined for years, and which is now proving tremendously useful against other diseases and in other research pathways. Where would we have been now in medical science if it had never been sidelined in the first place? How many lives lost to COVID might have been spared?

The scientific method is a robust way of building knowledge, but it takes time, and undergoes extensive revision as later generations of researchers revisit and falsify earlier data. Meanwhile, most journalism, especially in an era of gutted newsrooms, collapsed topical beats, the decline of job security and income (requisite for proper investigative reporting), and immense pressure to contrive clickbait to keep businesses alive, moves quickly and declaratively.

We’ve also just undergone an extremely bizarre period for information sharing, in the form of contemporary social media: a grand experiment in town hall discourse that has also been guided and leveraged by private enterprise, amplifying the prevalence of outrage, clickbait, and hotbeds of extremism in our news cycles.

READ: Twitter’s Elon Musk debacle raises serious questions about digital citizenship

There are no easy answers as to how we’ll now strive to cultivate better. But we can start with ourselves, and our immediate communities. We can improve the care we give to stories offering sensationalist depictions of scientific advances. Every time there’s dramatic reporting on medical breakthroughs, journalists need to keep in mind that they are inflating hopes for desperate families, or twisting the knife for those who better understand a given breakthrough’s mixed results.

We, in signal-boosting such content, must do the same.

You don’t have to become an expert on every subtopic, but if something seems wildly hyped by mainstream or social media, it helps to look at a major article and see if it links to the original study. If it doesn’t, see if you can track it down, and pay attention to the type of trial listed (early phase, later phase? randomized and double-blind?), as well as the population size for participants. Check for disclosure statements, too: Where’s it coming from? Who’s sponsoring the research? And for a bit of added fun, do a key-term search to see if this is really breaking news, or something that has been in the works in the field for a while.

None of us, and none of our institutions, is ever going to get it right all of the time.

But part of embracing a more humanist lifestyle is approaching media literacy the same way we do the scientific method itself: less with an interest in grand shows of disillusionment whenever errors emerge, and more with the expectation that correction and refinement is just part of the process.

Modern medical research is unfolding in remarkable, life-changing ways.

Let’s give our chatter about it the dignity and care it deserves.