Dudnyk's Tim Anderson on the Enduring Value of Chemotherapy in Cancer Care

In the new age of innovative oncology therapies, chemotherapy still plays a critical role in cancer care.

I remember the day like it was yesterday: a former colleague, working at a competitive agency, disparaging the particular therapy I was working on because it was a chemotherapy. Boasting about how chemotherapy was on the way out and it was only a matter of time until cancer care would be would compromise of monotherapy and combination therapy with targeted agents only. To be fair, this was during the early 2000s when the likes of Herceptin and Avastin were making waves, and rightfully so, given the clinical benefits they were demonstrating across an array of tumor types. With targeted agents and precision medicine still in their clinical infancy, however, I recall thinking that chemotherapy in oncology care still had a long road ahead.

Here we are today, 15 years later, and I find myself at these past year’s ASH and ASCO conferences confronted once again with this very same question: Are we nearing the end of reliance on chemotherapy in oncology? The reemergence of this question means that something much more dramatic is happening in oncology. With the emergence of next generation sequencing and of innovative treatment approaches including immunotherapies, cellular therapies, and targeted agents, pharmaceutical companies and oncologists can provide life-changing results for more patients than ever before. The natural inclination is to propose ways we can usher in more of the “new” and usher out the “old.” Chemotherapy is synonymous with treatments of the past, and although it can produce significant responses, both as monotherapy and in combination with targeted agents, it comes with a sort of off-target toxicity tax that is perceived as primitive.

However, chemotherapy still is likely to play a significant role in many cancers ­– both in solid tumor and hematologic malignancies – well into the future. One of the main reasons is the complex heterogeneity of cancers. The high degree of diversity in diseases such as breast cancer and acute myeloid leukemia (AML), for instance – and among individual patients – has become increasingly clear over the past years. Because of this heterogeneity, several factors must be evaluated when assessing risk of disease progression and treatment resistance in order to select an appropriate course of therapy.

When we look at HER2+ breast cancer, targeted therapies such as trastuzumab and pertuzumab have made a significant impact on countless women facing early stage breast cancer and advanced HER2+ breast cancer. And, when we consider innovations in cancer treatment, chemotherapy is still a foundational component in neoadjuvant, adjuvant, and metastatic treatment. Additionally, we are seeing innovation in metastatic breast cancer in tandem with (rather than in spite of) chemotherapy.  For example, I recently was inundated with online articles touting the potential of new therapies that “could replace chemotherapy with fewer side effects.” After taking a closer look, though, I realized that the authors of these articles were referring to the potential anti-body drug conjugates, commonly referred to as ADCs. Although ADCs have entered the marketplace (with many more in development), I was confused by such a claim.  Simply put, an ADC combines monoclonal antibodies specific to surface antigens present on tumor cells with ­a highly potent cytotoxic agent (ie, chemotherapy). ADCs target specific cells, which can potentially lead to less toxicity. But it is misleading to the community – especially patients ­– to position ADCs as non-chemotherapeutic when chemotherapy still plays a critical role in the innovative aspect of these new agents.

Treatment approaches in AML are undergoing significant changes after nearly 4 decades of stagnation in which the treatment paradigm was delegated by patient fitness. Hematologists/oncologists first evaluated a patient’s fitness for a chemotherapy regimen and if a patient was deemed “fit” they received a combination chemotherapy that included an anthracycline. Multiple novel therapeutic agents for AML have been evaluated in the past decades and have shown limited meaningful clinical improvement in outcomes.  With the recent approval of new therapies, particularly targeted agents (eg, IDH1/2 inhibitors, FLT3 inhibitors, BCL-2 inhibitors, etc.), a new era in AML treatment is upon us, affording oncologists the opportunity to better select treatments for patients based on disease biology.

However, AML is also a heterogeneous disease with multiple molecular pathways driving its progression with 5-year survival rates at approximately 5%. The inherent complexity of the disease prompts treaters to evaluate the various disease and patient characteristics, knowing that each patient is unique and subpopulations of eligible patients for many of the new targeted AML agents are not mutually exclusive. Thus, some patients may be eligible for a combination of multiple therapies that have yet to be validated in a clinical trial setting. This is where chemotherapy still plays a significant role in the treatment of AML. Although AML is certainly no longer a one-size-fits-all approach, chemotherapy is still a foundational treatment intended to help achieve a complete remission in patients. Although complete remissions are more accessible in many younger patients, the goal of remission presents a much more significant challenge in older patients, of which constitute the majority of AML cases. When striving for a cure of the disease, chemotherapy may offer the best chance to induce a complete remission and transition patients to post remission transplantation.

The rate of innovation in oncology, with the introduction of new and targeted agents, has been life-changing for so many patients and families battling cancer.  With the arrival of such innovation in the market, it is understandable that some people are ready to move on from what is often perceived as a “treatment of the past.”  However, as I think back 15 years ago and fast-forward to this past ASH and ASCO, despite the occurrence of these major breakthroughs, the future of chemotherapy is solidified through its continued utility across various stages of solid tumors and hematologic malignancies. In fact, projections in a recent publication show that the number of patients requiring chemotherapy is expected to increase by more than 50% from 2018 to 2040 (if all patients requiring chemotherapy are treated)1. Although the days in which frontline chemotherapy was the only available treatment option are gone, chemotherapy still plays a critical role both in curing many cancers and in significantly prolonging so many patients’ lives.


Reference:

  1. Wilson BE, Jacob S, Yap ML, et al. Estimates of global chemotherapy demands and corresponding physician workforce requirements for 2018 and 2040: a population-based study. Lancet Oncol. 2019;20(6):769-780.