The American Association for Cancer Research (AACR) 2022 meeting was held in New Orleans from April 9 to 13. Doctors and researchers worldwide joined together virtually and in person to make this year’s meeting one of the largest gatherings since the start of the pandemic. They shared the many exciting developments in cancer research and treatment that emerged over the last year. This year’s meeting is another testament to “Science doesn’t stop, and scientists never sleep!” Here, we discuss some of the major highlights of the meeting.
Cancer Interception and Early Detection: A major theme at this year’s meeting was cancer interception – catching cancer at its earliest stages and stopping it from progressing. This year’s conference highlighted work from the SU2C-American Lung Association – LUNGevity Lung Cancer Dream Team. Cancer develops sequentially as normal cells become premalignant lesions (PMLs). Some of these then progress to form lung cancer. By comparing PMLs that do not progress to cancer to those that do, the Dream Team has found that immune cells are more abundant in PMLs that don’t advance. This finding suggests that the immune system is important in keeping cancer at bay. It also indicates that immune interception may be a potential option in the future as we develop more and more tools to understand what drives a PML into becoming cancer. This work also lays the foundation of the Pre-Cancer Genome Atlas – a multi-institutional, global collaboration to study these premalignant lesions in tumor types, including lung cancer. The PCGA will help us understand why PMLs become cancer at a molecular level. More importantly, it will also help us know which individuals will need to be monitored more carefully and possibly be good candidates for interception. Of course, there was discussion around blood-based multi-cancer early detection tests (MCEDs) – “one-stop-shop” blood tests that can detect multiple cancers at the same time. While the prospect is very exciting based on data from early trials, there is more to come on this front! It is important to keep in mind that when available, these tests will be used in the normal screen-eligible population – adults between the ages of 50/55 and 80.
Targeted Therapies: This year’s AACR was a big one for advances in KRAS. Results from the 2nd year of analysis of the CodeBreaK 100 trial, looking at the effect of the KRAS inhibitor sotorasib in patients whose tumors had a KRAS G12C mutation, were presented. One-in-three patients (32.5%) were alive after two years on the drug, a notable improvement compared to patients receiving only chemotherapy (8%). Very exciting, indeed! Results from another KRAS G12C inhibitor, JDQ433, were presented as part of the KontRASt-01 trial, and the early data look promising. There was also lots of discussion about targeting non-G12C mutations and developing pan-RAS drugs. For more information, please check out our separate blog here.
Three-year follow-up data from the CROWN trial looking at crizotinib versus lorlatinib as first-line treatment in patients with ALK+ lung cancer was striking. 81% of patients’ tumors had progressed on crizotinib versus 36% on lorlatinib. Lorlatinib is definitely the new standard of care for this patient group! We also saw developments in the EGFR space, such as BLU-945, a new targeted agent aimed at inhibiting double-mutant or triple-mutant EGFR (T790M or ex19del/T790M/C797S) cancer.
Immunotherapy: This year’s other big winner was immunotherapy – specifically, immunotherapy for treating early-stage (stage IB to IIIA) non-small cell lung cancer (NSCLC). Traditionally, patients with this disease were offered surgery with/without chemotherapy. However, the chances of the cancer coming back were quite high. The FDA recently approved using the immunotherapy drug, nivolumab, in combination with platinum-doublet chemotherapy as a neoadjuvant treatment (given before surgery) to shrink the cancer before surgery. Results from the Checkmate-816 trial that led to this approval were presented at AACR. In patients receiving the combination, median EFS was 31.6 months, compared to 20.8 months for patients treated with chemotherapy alone. EFS, or event-free survival, is a measure that researchers use to understand clinical trial results in the neoadjuvant setting. A higher EFS means that the patient did not have any complications from the treatment before surgery, did not have to delay surgery, and did not have major complications post-surgery. The combination was much better than chemotherapy, leading to the FDA approval.
Another neoadjuvant trial, NeoCoast, looked at combining the PD-L1 blocking antibody, durvalumab, with novel immunotherapies such as olectumab, which blocks CD73, or monalizumab, which blocks NKG2a, or danvatirsen, which blocks STAT3, showed similar results. It showed that adding immunotherapy before surgery may be a potential treatment route for early-stage disease. As of now, two immunotherapies are approved for early-stage NSCLC: nivolumab + chemo before surgery or chemo + atezolizumab after surgery (adjuvant treatment). Doctors should make the ultimate choice of immunotherapy by considering patient preferences. New therapies like these also highlight the need for a multidisciplinary care team for early-stage NSCLC. This team should include a medical oncologist, a surgical oncologist, and a radiation oncologist. We also saw some early results on using cell-based immunotherapies, such as CAR-T cells and TILs (tumor-infiltrating lymphocytes) in NSCLC. While it’s too early to make claims, it is great to see doctors explore these newer options in patients. It’s particularly exciting for patients whose tumors have an EGFR mutation and that do not respond/have stopped responding to standard immunotherapies like PD-L1-blocking drugs.
A special note of gratitude to the patient community and their family members! Without their trust in science and sense of community, these clinical trials would not have been possible. Thank you for helping push science forward.
Please join us for our next update—news from ASCO 2022.