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4. January Newsletter

Newsletter 1: January 2023

 

Welcome. The beginning of a new year is a good time to take stock of where things stand, as well as to look at the highlights of the year that has just passed.

We start by looking at the annual US cancer statistics which have just been published by the American Cancer Society (ACS); these help us to look at the latest ‘big picture’ view.

And there is some good news.

The death rate from cancer in the US is declining

Cancer is a scary disease. We are constantly seeing news of people who have recently been diagnosed or may have succumbed to the disease. So, you may be surprised to learn that the primary message from the latest cancer statistics update[i] is favourable. Their headline statement is: “The cancer mortality rate has decreased continuously since 1991, resulting in an overall drop of 33% and approximately 3.8 million cancer deaths averted”.

What are the main drivers of this favourable trend?

·       By far the biggest factor is the decline in smoking and the associated lung cancers, particularly in males; a trend which, having grown explosively from the 1930's, then peaked in 1990 and has been declining significantly ever since.

·       Another factor is the introduction of screening and early detection, especially for breast, prostate and colon cancers; routine screening these cancers was introduced in the US in the latter half of the 1980’s and the first half of the 1990’s.

·       Thirdly, the ever-advancing improvements in treatments; which is now accelerating with the latest advances in the developing modalities of targeted treatments and immunotherapy (more on this in the highlights section below).

Digging deeper into the stats there are, however, some issues.

·       Breast cancer incidence is rising.  The ACS reports that this is attributed, at least in part, to “continued declines in the fertility rate (having fewer children, or having their first baby after age 30) and increases in excess body weight”.

·       There has been an uptick in new prostate cancer cases. Of particular concern is the proportion of men diagnosed with more advanced or distant-stage disease, which has doubled since 2011. This is mainly attributed to the scaling back of PSA-based screening from around 2008, a result of concerns about overdiagnosis (see reference [ii] for example).

·       A declining trend in colon cancer mortality rates masks an increasing trend in young adults diagnosed with the disease. This rising trend in the US and several other high-income countries since the mid-1990s remains unexplained but likely reflects changes in lifestyle exposures (such as dietary habits and rising obesity[iii]).

There is also an opportunity:

·       In some good news, data from women ages 20 to 24 who were first to receive the vaccine for the Human Papillomavirus (HPV), showed a 65% reduction in cervical cancer incidence rates from 2012 through 2019. This offers strong support to the WHO goal to eliminate cervical cancer as a disease through global vaccination by 2030[iv].

 

And there is an unknown:

 

·       Looking ahead, the ACS report states that delays in diagnosis and treatment arising from the COVID pandemic may lead to an uptick in advanced-stage disease and mortality; and that these and other secondary consequences of the pandemic will occur gradually over time and will require many years to quantify at the population level because of the 2-year to 3-year lag in population-based cancer incidence and mortality data.

 

Treatment advances continue to be dominated by targeted therapies and immunotherapy

 

1.       There was a significant expansion in targeted “smart bomb” drugs.
The basic rationale for chemotherapy is that it kills all fast-dividing cells. Most cancer cells are indeed fast-dividing, but so are some healthy cells (e.g. hair, lining of the gut, immune cells etc). So, there is usually collateral damage, sometimes significantly so. Is it not possible to just target cancer cells? This is the thinking behind smart bomb drugs - an engineered drug consisting of a "homing-device" (to find and lock onto cancerous cells) linked to a pay load, for example a chemotherapy or radiation pellet (to then destroy these cells). This then enables the more precise delivery of conventional drugs to increase killing effectiveness and to reduce collateral damage. Although not an entirely a new technology, there was a significant increase in "smart bomb" options for use in more resistant cancers during 2022:

1.1.   In breast cancer there are now approvals for chemo-based Antibody-Drug Conjugates (ADC’s) for resistant breast cancers - covering resistant Her2-positive cancers, a new category called Her2-low disease, as well as the difficult to treat triple-negative breast cancer[v].

1.2.   There is also a new approval for a "radioligand" (using a radiation pellet for payload) for a target commonly found on many prostate cancers[vi].

 

2.       Advances in Immune oncology (IO) continue to dominate the headlines

2.1.   At last, significant IO responses obtained in some colon cancers:
IO for colon cancer has generally been disappointing up to now. But there is a subcategory of colon cancer which is caused by damage (sometimes inherited) to DNA repair genes – so-called dMMR colon cancer. This damage results in highly mutated cancer cells, and these are then significantly responsive to IO. Responses have been more than encouraging[vii] – it is not often that there is a standing ovation in response to a presentation of results of a trial at a major oncology conference.

2.2.   Using IO in earlier-stage disease.
Immunotherapy was initially approved for the treatment of advanced cancers. But it is increasingly proving successful in the treatment of earlier-stage cancers - where it is used prior to surgery (called neoadjuvant therapy), to help prevent disease recurrence[viii].

2.3.   A personalised mRNA cancer treatment vaccine
You may have heard about mRNA technology which was used in the remarkably successful development of COVID vaccines. This same technology is now being adapted for use as a cancer treatment vaccine. Why is this interesting?

Cancer immunotherapy using the new checkpoint inhibitor drugs can be remarkably effective, even for advanced cancers. But sometimes (quite often, actually) they do not work very well and need some help. This is where the new treatment vaccine could help.

The mRNA technology can be used to personalise a treatment vaccine for any given specific tumour. This entails extracting cancer cells from the tumour, analysing these cells to identify mutations unique to that cancer, and then using mRNA technology to develop a vaccine specific to these mutations.

The vaccination then helps to alert and expand immune cells in the body specific to the tumour; thereby increasing the capacity of the immune system to attack the tumour in support to the checkpoint inhibitor treatment.

Trial results of this approach showed a reduction in the risk of recurrence or death among melanoma patients of over 40% as compared to a standalone IO checkpoint inhibitor therapy[ix].

 

3.       In conclusion

The death rate from cancer is declining, and the conveyer belt of new treatments never stops.

There is reason for hope.

May the New Year be good to you.

 



[i]  The full report is Cancer statistics 2023, American Cancer Society, January 2023 and is summarised here.

[ii] PSA and Prostate Cancer: Between Guidelines and Practice - Medscape - Dec 09, 2022.

[iii] Early-Onset Colon Cancer Projected to Double by 2030 - Medscape - May 12, 2022.

[iv] Reaching 2030 cervical cancer elimination targets - WHO recommendations

[v] Antibody-Drug Conjugates (ADCs) for Breast Cancer: 5 Things to Know - Medscape - Nov 11, 2022.

[vi] FDA Approves New Radioligand Therapy and Diagnostic for mCRPC - Medscape - Mar 24, 2022.

[vii] 'Great Optimism' Over Complete Responses in dMMR Rectal Cancer - Medscape - Jun 05, 2022.

   Unprecedented' Responses to Neoadjuvant Treatment in dMMR Colon Cancer - Medscape - Sep 11, 2022.

[viii] Preop Nivolumab Plus Chemo 'a Quantum Leap' in NSCLC Therapy - Medscape - Apr 12, 2022.

   Not Just What, But When: Neoadjuvant Pembrolizumab in Melanoma - Medscape - Sep 11, 2022.

[ix] 4 Things to Know About Moderna's mRNA Cancer Vaccine - Medscape - Dec 16, 2022.