ASCO 2022: Striving to Ensure No Patient is Left Behind

By Karson Kump, Consultant

Aside from the plenary presentations, there were promising data illuminating hope for cancer patients everywhere you looked. Here are just a few additional study results that were presented:

• Neoadjuvant “immunoblative” treatment in MMRd Stage II/III rectal cancer with dostarlimab (anti–PD-1) had a 100% complete response (CR) rate in 12 patients and zero grade 3+ adverse events (AEs). Larger studies are needed before this becomes paradigm changing, but hard to ignore a 100% CR rate!
• The pivotal Phase II glofitamab (CD3xCD20 bispecific) study in heavily pretreated relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) patients hit its primary endpoint with a 39% CR rate (with CRs lasting a median of 34 months). This provides a promising option after CAR-Ts or in patients who cannot access them.
• Serplulimab is the first anti-PD-1 to improve OS in extensive-stage small cell lung cancer (SCLC) when combined with chemo (15.4 months vs. 10.9 from chemo + placebo). This is likely to become the frontline option for SCLC patients.
• Pembrolizumab + ramucirumab is the first non-chemo backbone combo to show survival improvement (14.5 vs. 11.6 months) in immune checkpoint inhibitor (ICI)-refractory non-small cell lung cancer (NSCLC) patients. This provides an additional line of IO-based treatment before resorting to chemo.
• Nimotuzumab (anti-EGFR) when added to gemcitabine increased mOS to 10.9 months (from 8.5 months in the comparator arm) in KRAS WT pancreatic cancer, with 44% of patients surviving one year (versus 27%). Although KRAS WT only accounts for 5-10% of cases, this shows that we should not ignore an opportunity to chip away at improving survival in this lethal disease.

Crafting More Personalized Treatment
Personalized medicine certainly had its presence at ASCO this year with a focus on refining our ability to elucidate each patient’s tumor to map the therapeutic course with the highest probability of success. Dozens of oral and poster presentations from companies such as Guardant, Tempus, and Foundation taught us that novel therapies can only take us so far and we need better strategies to elucidate each patient’s tumor. Integrating multiple data points like DNA/RNA sequencing and real-world data will provide the best visibility to make sure each patient gets the best treatment.

Minimal residual disease (MRD) analysis via circulating tumor DNA (ctDNA) testing is an exciting arena in early-stage solid tumors and is poised to help answer the great adjuvant debate, “to treat or not to treat?” The DYNAMIC trial in Stage II colon cancer illustrated the impact of ctDNA by using MRD+ status to guide adjuvant treatment leading to a ~50% reduction in adjuvant chemotherapy use (28% to 15%) with no impact on recurrence free survival. These results teach us that sometimes less is more (or equal…) and can spare patients from the unnecessary toxicity of adjuvant chemo. The utility of MRD was demonstrated across an array of tumor types including head & neck cancers, NSCLC, breast cancers, and sarcomas. ctDNA and MRD developments are rapidly accelerating and are sure to continue to improve adjuvant and recurrence monitoring patient management.

A quote that stood out from the week was “patients are the experts on their own experience,” which set up the need for more usage of patient reported outcomes (PROs). The previously reported randomized control trial (RCT) results using the PRO app, Moovcare, were discussed and show that non-progressive Stage III-IV NSCLC patients who followed up weekly with Moovcare experienced a 7-month mOS improvement compared to those who stuck with standard of care reporting. This teaches us that patients cannot just be pumped full of drugs and then just “watch and wait,” they need to be constantly monitored with an immediate plan of intervention when signs of decline are signaled.

Addressing and Tackling Disparities
This year’s theme was “Advancing Equitable Cancer Care Through Innovation,” and disparities across the board were rightfully highlighted throughout the sessions. On the main stage of the plenary the presentation of the DETERMINATION trial called out the African American disparities in oncology which are possibly the most acute in myeloma. Despite incidence rates of myeloma being twice as high with diagnosis 5 years earlier in African Americans compared to white patients, they are underrepresented in clinical trials, making it difficult to answer the question of Black patients, “are these clinical data applicable to me?” The DETERMINATION trial set a new bar with the highest fraction of African American patients enrolled in a Phase III myeloma trial, representing 19% of patients. The most shocking disparity is that despite the recent survival improvements in myeloma, African American patients still face an OS that is half that of white patients, primarily driven by lack of access to the “Four Ts” (Triplets, Transplants, Trials, and CAR-Ts) which is especially poignant given the fact that when access to treatment is equalized, African Americans survive at similar (if not better) rates.

It is not enough just to talk about the problems, so it was encouraging to see a presentation that explicitly showed how a 10% increase in state welfare spending led to an 8.6% increase in OS for African Americans, which translates to closing the disparity gap with white patients by ~45%. The presenter, Dr. Justin Barnes (University of Washington Medical School), concluded with, “the main message is actually relatively straightforward and simple—disparities can be impacted by investing in programs that address the social determinants of health.”

While there is a myriad of reasons why we are plagued with racial and socioeconomic disparities in oncology (and society in general) the bottom line is that they are unacceptable, and it is invigorating to see them acknowledged head on with actionable plans to narrow the gaps.

Conclusions

• Therapeutic efficacy continues to be improved with novel therapies and combinations across a wide range of tumor types in the frontline and relapse/refractory settings, which leads to lives saved, one at a time.
•  Therapeutic breakthroughs do not need to be confined by pre-defined patient segmentation and discoveries can re-define how subgroups are classified to ensure no patient falls through the cracks and can get the most effective treatment possible.
•  No patient sub-segment should be neglected; if there is a way to improve survival, no matter how small the population, it is worth it.
•  Novel diagnostics and technologies will continue to elucidate personalized treatment plans and enable patients to have a voice in their own experience.
•  Disparities in oncology care are real and unacceptable and they need to be confronted with action, even if it sacrifices the efficiency of clinical development, to make sure that no patient is left behind.

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Karson Kump is a consultant based in the Boston office and works primarily in the biopharma and precision medicine practices.

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