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March 15, 2017

Cancer Progress and the Budgetary Wolf

Promising Approaches to Treating Cancer Stalked by Cost Constraints

Cancer Progress and the Budgetary Wolf

Scanning electron micrograph of pancreatic cancer cells grown in culture. [NIH]

  • The recent Cancer Progress event proved to be a surprisingly cheerful event, with most presentations accentuating the positive—the “Progress” in Cancer Progress—and expressing optimism that the negative—the “Cancer”—may be brought under control, eventually.

    Yet prowling the edges of many presentations was something dark and dangerous. And it wasn’t, as you might expect, the fear that cancer would, once again, find new pathways of resistance and relapse. No, the source of dread wasn’t the sense that cancer biology was too complex or human knowledge too limited. Rather, it was the sense that unseen budgetary nooses were tightening, threatening to strangle the life out of promising new approaches such as checkpoint inhibition, next-generation functional diagnostics, anticancer vaccines, and combination therapies.

    All too aware of this ominous possibility, the Cancer Progress presenters could hardly avoid commenting on it now and then, even during discussions that were nominally and substantively technical in nature, not financial. For example, during a panel on exceptional responders, Memorial Sloan Kettering’s David Solit, M.D., complained that while genomic testing could match cancer patients with potentially life-saving clinical trials and suitable drugs, there remained a lot of “inequality and randomness” in the availability and distribution of resources—the tests, the interpretive expertise, and the drugs themselves.

    Other speakers bemoaned the neglect of combination therapies, a neglect attributable, in part, to an unwillingness to evaluate “off label” drugs, not just because of the risks of adverse interactions, but because of the fear of accepting unreimbursed expenses. More generally, straightened finances were seen to discourage the trial-and-error probing of cancer, a severe constraint, given the individuality of each patient’s cancer. How many insights might be lost, some speakers wondered, if patients best suited for small, personalized trials were instead herded into large and ostensibly cost-effective trials? Might subtle but telling responses be lost in the statistical din?

    When asked to speculate about how the development and approval of new therapeutic entities might proceed in 2025, Edith Sanford Foundation’s Brian Leyland-Jones, Ph.D., and the Moores Cancer Center’s Razelle Kurzrock, M.D., expressed the hope that early disease evaluation would encompass not just genomics, but epigenomics, transcriptomics, and proteomics, including glycosylation status. These scientist-clinicians also asked, what good would all the evaluation technologies be if they remained inaccessible or unaffordable, or if they were to be meted out sparingly, say, during end-stage disease?

    While many of the speakers alluded to funding constraints, none of the expressions of concern was long sustained, not until the final session, Cancer Drug Pricing: Valuing the Value of Innovation. Instead, anxious words faded away almost as soon as they emerged, rather like a musical figure hinting at developments to come later in a large and varied symphonic composition. Think of the symphonic fairy tale, Peter and the Wolf, which contrasted a jaunty tune, representing the adventurous Peter, and an ominous theme, representing the skulking, ravenous wolf.

  • The Price of Everything

    During the pricing panel, the darkness that was at the edges of the scientific discussions was fully realized, with Memorial Sloan Kettering’s Peter Bach, M.D., citing “financial toxicity,” Humana’s Roy Beveridge, M.D., warning of a “race to the bottom,” and Real Endpoints’ Roger Longman weighing the prospects for “value-based pricing.” Overall, the discussion suggested that an already-uncertain economic picture is being further clouded by new political developments.

    Through the murk, however, there appear to be a few hard truths. As much as value-based pricing may be desired, it remains elusive because head-to-head comparisons of similar drugs, administered to similar populations, are generally lacking, leaving scope for competition among alternative frameworks, a competition sure to be closely watched by stakeholders holding disparate degrees of market power. Ultimately, the hardest truth may be that all stakeholders—taxpayers, employees, employers, insurers, or fiscal guardians—generally feel the pain of expenditure immediately and directly. They must exercise a little imagination to appreciate cancer research and clinical development as collective undertakings that bestow universal benefits.

    Framing matters. An example of a narrow frame, described by Dr. Bach, would weigh a $2 billion therapy against its benefit for a “small population.” Within this frame, one could “do the math” and arrive at the unsurprising (and uninspiring) result.

    A broader view would be more supportive of continued investment in cancer progress, but only if aggregate returns were to escalate as quickly as costs. Yet, statistics about cancer progress are debatable, Dr. Bach noted, and even now, most credit for improved outcomes appears to be due to lower smoking rates. In any case, Dr. Bach concluded, current pricing trends are “not necessarily sustainable.”

    And so, the conference’s last panel ended inconclusively. A similar panel could be convened next year, and the year after that, in the manner of a game of musical chairs, except that all the chairs are kept in place. While this game continues without resolution, it will grow more frenetic, as though it were keeping time with a rising musical tempo.

    Fortunately, Cancer Progress offered numerous opportunities to turn away from the mad round, and the threat of exhaustion, in its scientifically oriented sessions. One session in particular illustrated how a fresh look at seemingly well-understood phenomena could yield surprising insights.

  • Living with Cancer

    In the session “Aging and Cancer: Live and Let Die or a Cancer-Free Methuselah,” the University of Colorado’s James DeGregori, Ph.D., and the Buck Institute’s Judith Campisi, Ph.D., revisited the age-dependent patterns of oncogenesis and found clues that mutation accumulation, the usual measure of cancer risk, was only half the story. Essentially, mutational burden and cancer onset do not appear to be related to aging in any simple way.

    The missing factor, Dr. DeGregori suggested, is the quality of the tissue environment, which is so ably maintained through youth, yet suffers as we age. In Dr. DeGregori’s models, “young” tissue environments and “old” tissue environments appear to present different mutational landscapes, such that mutated cells are maladapted to the former, but more apt to survive in the latter. If we pay more attention to the tissue landscape, Dr. DeGregori suggested, we might feel moved to extend “Marshall Plans” to cancer patients when they are recovering from treatment.

    The translational potential of modulating the tissue environment was also taken up by Dr. Campisi, who focused on the accumulation of senescent cells with age. These cells can tilt tissues toward cancer because the senescence associated secretory phenotype (SASP) tends to drive inflammation. Rather than conclude that senescent cells should be eliminated, or SASP should be suppressed, Dr. Campisi emphasized the need to distinguish between SASP’s worst manifestations, and SASP pathways that help sustain normal tissue homeostasis and contribute to helpful functions such as wound healing.

    By depressing selected pathways and/or replacing certain missing secretory factors, anticancer interventions might succeed in slowing cancer, if not eliminating it. Such interventions might enhance ones chances of becoming a centenarian, a status that by no means demands perfection. As Dr. Campisi noted, deceased centenarians, at autopsy, are more likely to be riddled with indolent or occult cancers than to be cancer-free.

    Living with cancer instead of eradicating it may seem less than a triumph. But triumph, utter and complete triumph, may be the stuff of fairy tales, like Peter and the Wolf, where the wolf is, of course, dispatched at the end. It may be enough that wolves, whether physiological or financial, are kept at some comfortable distance, and not allowed to lurk at the door.

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