Attending the annual American Society for Clinical Oncology (ASCO) meeting, held in Chicago after Memorial Day each year, has become a favorite annual ritual. For me, it almost signals the beginning of summer, with healthy doses of hope and expectations about all the newest developments in lung cancer research into early detection and treatment. I returned from ASCO last Tuesday, and believe it or not, it took me this entire past weekend to sift through copious scrawled notes and blurry iPhone photos and write this blog. This year, around 38,000 doctors and researchers from all over the world congregated in the Windy City to discuss the latest developments in cancer.
ASCO is held at the McCormick Convention Center in Chicago, the largest convention center in North America (to give you some context), so I was incredibly lucky to run into so many of our Scientific Advisory Board (SAB) members and awardees. LUNGevity has funded 118 lung cancer research grants since 2002. Forty-seven of the researchers on these grants contributed to lung cancer research projects being presented at the 2017 ASCO conference. In addition, 12 of our 20 SAB members contributed to research presented at this year’s meeting.
Now comes the hardest part – how to distill all that information into three key themes (I have been trying to stick to three) and do justice to all this information? This year’s ASCO had so much information that three themes will not capture it. I am going to use six themes!
This year was a big one for targeted therapies. For patients whose tumors test positive for EGFR mutations, we may have another first-line option in dacomitinib, a second-generation EGFR tyrosine kinase inhibitor (TKI). In a clinical trial, dacomitinib was superior to the first-line drug gefitinib (Iressa®). However, it should be noted that it also came with more side effects.
Osimertinib (Tagrisso®), a third-generation TKI, in second-/third-line treatment continues to show promise in patients who have progressed on prior EGFR-blocking drugs. More importantly, data presented at ASCO showed a clear benefit of this drug on brain metastasis, a problem that earlier TKIs could not solve because they cannot penetrate the brain.
Patients with ALK-rearranged lung cancers have big news coming their way! ALK TKI alectinib (Alecensa®) proved to be superior to crizotinib (Xalkori®), the current standard of treatment, in both the primary lung cancer and brain metastasis. Alectinib is on its way to becoming the new standard of care for ALK-positive patients in the first-line setting. Another ALK TKI, lorlatinib, continues to show promise in clinical trials, where it is highly effective in situations where the ALK gene undergoes mutations.
I am always amazed at how scientists come up with new tools each time a cancer cell mutates. Speaking of new tools, now we know how cancer cells are escaping the effects of osimertinib: by acquiring a mutation in the MET gene. Soon combination treatments with a MET inhibitor and an EGFR inhibitor may be useful in such patients.
As always, immunotherapy continues to make strides. Long-term follow-up data on pembrolizumab shows that in those lung cancer patients in whom immunotherapy works, the response is long-lasting. This is the second report that responses from immunotherapy are durable. Also, LUNGevity Scientific Advisory Board member Dr. Julie Brahmer discussed that chemotherapy given after progression on immunotherapy may be more effective than just chemotherapy alone. This may happen because the administration of chemotherapy after immunotherapy may block tricks that cancer cells use to hide from the immune system, making the immunotherapy more effective. The theme was rational combinations – when and how to sequence immunotherapies with another immunotherapy or another drug.
Of course, no conference is complete without a discussion on immunotherapy biomarkers, how we can predict which patients will benefit from immunotherapy. Data presented at ASCO demonstrate that PD-L1 staining alone may not be sufficient; rather, a combination of PD-L1 staining of the tumor and tumor mutation burden (TMB – the number of mutations in the DNA of the cancer cell) may be a more accurate predictor. I was also pleased to see presentations that discussed how side effects of immunotherapy are equally important in determining which patients should receive immunotherapy.
Small cell lung cancer
This brings me to the discussion on small cell, a subtype of lung cancer that has not seen much treatment progress. Data on combination immunotherapy using a PD1 (nivolumab) inhibitor and a CTLA-4 (ipililumab) inhibitor in the second-line setting in patients with small cell lung cancer look promising. Both PD1 and CTLA-4 are immune checkpoints that cancer cells co-opt to hide from the immune system. The ipi-nivo combination was given to patients who had progressed after their initial chemotherapy. While the side-effect profile of this combination may determine which patients would receive it, this is the first account of immunotherapy being beneficial in patients with small cell lung cancer. Other approaches, such as chemotherapy with a PARP inhibitor, continue to move ahead in the trial process.
Treatment of elderly lung cancer patients
Often clinical trials do not include patients who are older than 70 years of age despite the fact that the median age of diagnosis of lung cancer is 70 years. I was really excited by discussions about how lung cancer therapies should be tailored to the age of the patients. Addition of cisplatin to the standard chemotherapy regimen did not provide substantial benefit versus doublet chemotherapy in elderly patients. Based on their health status, elderly patients may also benefit from immunotherapy.
Yes – it’s happening! You will notice me discussing liquid biopsies more and more in my blogs. No oncology conference is complete without a session on these new technologies. LUNGevity Scientific Advisory Board member Dr. Alice Shaw pointed out that liquid biopsies are entering clinical practice for the management of non-small cell lung cancer. Current liquid biopsy technologies can (1) detect druggable mutations in the blood of lung cancer patients at the time of diagnosis, (2) identify mutations that confer resistance to targeted therapies after there is a recurrence, and (3) help monitor response to targeted therapies and predict clinical outcomes. Researchers are continuously improving upon these technologies to make them more accessible to lung cancer patients. There were also discussions on how liquid biopsies may, in the future, help identify patients who will benefit from immunotherapy. Lots to come from this arena!
I was thrilled to see lung cancer patient advocates in conference sessions discussing what patients value from their treatments and how patient engagement should factor in deciding cost of oncology drugs. Also, data on how patients using a chemotherapy side-effects reporter felt better and had a better outcome highlighted the fact that patients who are equal partners in the healthcare decision making are empowered and have better outcomes. This should explain this year’s ASCO theme – Making a Difference in Cancer Care WITH YOU – where WITH YOU includes the patient!
ASCO 2017 was indeed a great way to start summer – with lots of excitement and hope. Looking forward to ESMO and World Conference on Lung Cancer this fall.
Dr. Basu Roy is LUNGevity's Director of Translational Research Programs/Director of Patient FoRCe.