This year for Lung Cancer Awareness Month #LCAM I’m going to summarize 30 important lung cancer trials over 30 days. These posts are directed at non-medical professionals, with descriptions of the results and of what makes a good trial.#lcsm 1/13
Lung cancer with an EGFR mutation is in some ways similar to the ALK mutations we discussed two days ago. It’s a type of lung cancer that tends to affect non-smokers, and accounts for around 4-5% of all lung cancers. Today’s trial was a pivotal advance in its treatment, from 2009
Early in the EGFR story we had drugs that inhibited the action of EGFR, but were not sure what test would best determine who would respond to those drugs. Expression of EGFR protein? Extra copies of EGFR gene? Changes (mutation) in EGFR gene? 3/13
This trial enrolled patients with advanced lung cancer and characteristics known to be associated with EGFR mutation: former or non-smokers of east Asian ancestry. They were randomized to receive either standard chemotherapy or the EGFR inhibitor Gefitinib (Iressa). 4/13
The primary outcome was time to the cancer worsening (progression-free survival, PFS). There was a planned subgroup analysis to look at those with and without an EGFR mutation. The trial design was for non-inferiority, a topic that we’ll cover at a later date. 5/13
PFS was slightly better with gefitinib in the whole study population (Panel A below).
But in the EFGR mutation subgroup median PFS was about 4 months longer with gefitinib (p<0.001 Panel B).
In the group with no mutation PFS was about 4 months longer with chemo (p<0.001 Panel C)
People with mutation who got gefitinib had greater improvement in quality of life and fewer side effects from treatment than people on chemo.
This trial established that presence of EGFR mutation is the correct test to identify those who will benefit from EGFR blocking drugs.
Given all the advantages of gefitinib, it may come as a surprise to hear that for patients with EGFR mutation the overall survival was the same in the two arms (21.6 vs 21.9 months, p=0.99). This is probably related to an important factor: cross-over 8/13
Cross-over is when study participants who were randomized to one treatment get the other treatment after study completion. For instance, in this study, 66% of patients with EGFR mutation on the chemo arm got gefitinib after their tumours progressed on chemo. 9/13
This suggests that people with EGFR mutation will get the survival benefit of gefitinib whether it's given as their 1st or 2nd treatment, as long as they get it at some point. Crossover is a reason why highly beneficial drugs may not seem to demonstrate a survival advantage.10/13
Trials like this one, and the crizotinib trial described 5 November, had an unexpected effect on lung cancer research: a population of long-living, reasonably well people with lung cancer is probably a prerequisite to the development of patient advocacy groups. 11/13
These groups, like @EGFRResisters, @ros1cancer, and @ALKCancer among others, have become powerful sources of community and advocacy for people living with cancer and their families, as well as increasingly influential research partners. 12/13
@TonyMok9 led this trial and is active on Twitter. We'd love to hear any comment or recollections.
I hope you’ll be back tomorrow when we’ll take our first look at a mesothelioma trial. See you then! 13/13
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For Lung Cancer Awareness Month #LCAM I’m going to summarize 30 important lung cancer trials over 30 days. These posts are directed at non-medical professionals, with descriptions of the results and of what makes a good trial. #lcsm 1/14
To date we have looked at trials that compared different treatments. Today, we’re going to look at something a little different: a trial of the schedule of supportive medications that are given along with chemotherapy, in this case vitamin B12 and folic acid with pemetrexed. 2/14
We have seen how pemetrexed has become one of the most commonly used chemotherapy drugs in non-squamous NSCLC (11, 13 November). Compared to other chemo drugs we think that it has a relatively good safety profile, but it was not always so. 3/14
November 14: Controversy, hierarchy
For Lung Cancer Awareness Month #LCAM I’m going to summarize 30 important lung cancer trials over 30 days. These posts are directed at non-medical professionals, with descriptions of the results and of what makes a good trial. #lcsm 1/17
This is the most recent study we’ve looked at so far, from 2020. You may recall that adjuvant chemotherapy (after surgery) increases the chances of cure for early stage lung cancer (Nov 2), and also that we have good oral medications for lung cancer with EGFR mutation (Nov 7, 12)
This trial enrolled people who had resected lung cancer with EGFR mutation. They were allowed to have adjuvant chemotherapy. They were then randomized to three years of the EGFR TKI osimertinib, or three years of placebo. 3/17
This year for Lung Cancer Awareness Month #LCAM I’m going to summarize 30 important lung cancer trials over 30 days. These posts are directed at non-medical professionals, with descriptions of the results and of what makes a good trial.#lcsm 1/17
The uptake of immunotherapy in lung cancer has been rapid and widespread. In 2014 it was research only: in 2021 it is used in all types of lung malignancies, in almost all stages of disease. We will discuss at least six immunotherapy studies in the remainder of the month. 2/17
Lymphocytes are white blood cells that should lead an immune response to tumours. In some cases, tumour cells have a protein on the surface called PD-L1 that binds to a protein called PD-1 on lymphocytes, and serves to “turn off” that part of the immune response. 3/17
For Lung Cancer Awareness Month #LCAM I’m going to summarize 30 important lung cancer trials over 30 days. These posts are directed at non-medical professionals, with descriptions of the results and of what makes a good trial. #lcsm 1/15
Today we are back to looking at EGFR-mutated lung cancer, with the FLAURA trial comparing osimertinib to either gefitinib or erlotinib in the first-line setting. Today’s discussion is from two papers, one looking at Progression Free Survival, the other at Overall Survival 2/15
You may recall from the IPASS study (7 November) that gefitinib improved PFS compared to chemo, with fewer side effects.
Erlotinib was another drug similar to gefitinib.
Osimertinib was the next-generation of EGFR drugs, with several potential improvements. 3/15
For Lung Cancer Awareness Month #LCAM I’m going to summarize 30 important lung cancer trials over 30 days. These posts are directed at non-medical professionals, with descriptions of the results and of what makes a good trial. #lcsm 1/11
Today we are back to looking at a study of chemotherapy for metastatic non-small cell lung cancer (NSCLC). Our last study in this area (3 November) established the notion that all platinum doublets were more or less the same. Today’s study, from 2008, overturned that consensus.
This was a trial comparing cisplatin-gemcitabine (standard) with cisplatin-pemetrexed. Pemetrexed is administered in a more convenient schedule than gemcitabine, and likely causes fewer side effects. Because of these advantages, the study was designed for noninferiority. 3/11
This year for Lung Cancer Awareness Month #LCAM I’m going to summarize 30 important lung cancer trials over 30 days. These posts are directed at non-medical professionals, with descriptions of the results and of what makes a good trial. #lcsm 1/15
To date in these tweets I have loosely used the term “lung cancer” to refer to non-small cell lung cancer (NSCLC), by far the commonest type of lung cancer. Today we’ll look at a trial in small cell lung cancer. 2/15
Small cell cancer is characterized by rapid growth and early metastasis. Initially very chemo responsive, it is resistant to treatments at the time of recurrence. If restricted to one side of the chest (limited stage) it can be treated with chemoradiation with a chance of cure.